- Tracheophyta
- Euphyllophyta
- Moniliformopses
- Equisetophyta
- Sphenopsida
- Equisetales
- Equisetaceae
- Equisetum
- Equisetum arvense (common or field horsetail) : sterols (b-sitosterol (60.0%), campesterol (32.9%), isofucosterol (5.9%) and cholesterol (trace amounts)ref) and isoquercitroside : antinociceptive and anti-inflammatory effectsref; dicaffeoyl-m-tartaric acid has vasorelaxant activityref, antioxidantref
- Lycopodiophyta
- Lycopodiopsida
- Lycopodiales
- Lycopodiaceae
- Huperzia
- Huperzia dalhousieana
- Huperzia serrata
- Spermatophyta
- Coniferopsida
- Coniferales
- Cupressaceae
- Juniperus
- Juniperus sabina
- Juniperus virginiana (a.k.a. red cedar)
- Pinaceae
- Pinus
- Pinus
- Pinus palustris (a.k.a. longleaf pine)
- Pinus mugo (a.k.a. mugo pine, Swiss mountain pine)
- Pinus mugo var. pumilio
- Taxaceae
- Taxus
- Taxus brevifolia
- Ginkgophyta
- Ginkgoales
- Ginkgoaceae
- Ginkgo
- Ginkgo biloba (maidenhair tree)
- Gnetophyta
- Gnetopsida
- Ephedrales
- Ephedraceae
- Ephedra (a.k.a. ma huang)
- Ephedra spp.
- Ephedra sinica (a.k.a. Chinese ephedra, cao ma-huang)
- Magnoliophyta
- eudicotyledons
- core eudicots
- Asteridae (asterids)
- campanulids
- Apiales; Apiaceae; Apioideae; apioid superclade; Angelica + Arracacia clade
- Peucedanum
- Peucedanum oreoselinum (a.k.a. oreoselinum) : a plant used in homeopathic practice as a diuretic.
- Asterales
- Asteraceae
- Asteroideae
- Astereae
- Aster
- Aster tataricus
- Plucheeae
- Sphaeranthus
- Sphaeranthus indicus is a rice weed commonly found in India, Sri Lanka, Africa and Australia, whose extract inhibits TNF-a and has been proposed as a treatment for rheumatoid arthritis
- Dipsacales
- Valerianaceae
- Valeriana
-
Valeriana
officinalis (a.k.a. common valerian) is used to treat insomnia
- Cornales
- Cornaceae
- Nyssoideae
- Camptotheca
- Camptotheca acuminata
- Ericales
- Ericaceae
- Ericoideae
- Rhodoreae
- Phyllodoceae
- Vaccinioideae
- Gaultherieae
- Leucothoe
- Leucothoe grayana
- Sapotaceae => gutta-percha [Malay getah perca sap of the percha tree] : the coagulated, dried, and purified latex of trees; used in orthopedics for fracture splints, in surgery for temporary sealing of cavities, and in dentistry in the form of cones for filling the root canal and in the form of sticks for sealing cavities over treatment.
- Styracaceae
- Styrax
- Styrax benzoin
- Theaceae
- Camellia
- Camellia sinensis
- non-fermented tea : green tea has a higher content of catechins (EGCG is 5 times higher in green than in black tea : old leaves > young leaves) and low caffeine
- semi-fermented tea : red tea (oolong tea) : the fermentation process during tea manufacturing reduces the levels of catechins and caffein significantly
- fermented teas
- black tea has higher caffeine and gallic acid levels
- Chinese pu-erh tea
- catechins
- (-)-epigallocatechin gallate (EGCG) binds to the metastasis-associated 67-kDa laminin receptor with a nanomolar Kd value
- (-)-epigallocatechin (EGC)
- (-)-epicatechin gallate (ECG)
- (-)-epicatechin (EC)
- theaflavins
- theaflavin (TF-1)
- theaflavin-3-gallate
- theaflavin-3'-gallate
- theaflavin-3,3'-digallate (TF-3)
- thearubigins
- gallic acid (GA)
- teine / caffeine / 1,3,7-trimethylxanthine / 3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6- dione / methyltheobromine / guaranine : there is 40-50 mg caffeine in a 160-ml cup of tea
- euasterids I
- Gentianales
- Apocynaceae
- Apocynoideae
- Apocyneae
- Forsteronia
- Forsteronia refracta : a nondescript member of the dogbane family found in the Amazonian rain forest
- Rauvolfioideae
- Alstonieae
- Alstonia
- Alstonia scholaris (dita bark, devil tree, pale mara) : in India the day of the new moon (Amavasya) in the month of July is considered to be highly auspicious. Various ancient rituals are practised on that day, one of which is drinking a herbal concoction prepared from the bark of the tree early in the morning on an empty stomach. The bark of this tree is collected fresh, well before the sunrise, and is ground up to make a herbal preparation called kashaya. This preparation is believed to cure and prevent bowel related disorders. Clinical uses of this tree have been well described in homoeopathic and ayurvedic literature. In 2004 as they usually did, 6 members of a family prepared kashaya, but this year making it from the bark of a relatively young tree. Within a few minutes, all of them had severe muscle spasms and started having convulsive movements. They were rushed to hospital, but the 2 children, aged between 6 and 8 years, were dead on arrival. The 4 adult members of the family were conscious but had muscle stiffness with periodic convulsive movements of the limbs and opisthotonos. The clinical picture was consistent with strychnine poisoning, and it was later confirmed that, in the dark, the family had taken the bark from Strychnos nux-vomica (strychnine tree) instead of Alstonia. Ancient traditions and rituals tend to abound with precepts and injunctions. To modern eyes, these can seem meaningless superstition, but much ancient wisdom can be hidden amidst such rituals. This family had blindly followed the ritual of taking kashaya but had neglected to follow the golden rule, to "Select only those trees with old scars on their trunk." This practice of selecting trees with scars on the trunk is the only sure and safe way to identify the correct tree in darkness; old scars on the trunk affirm the tree's use in the previous year. Had our patients followed this tip, identification of the right tree would not have been difficult, and the tragedy could have been avertedref
- Tabermontantaneae
- Tabernaemontana
- Tabernanthe
- Tabernanthe iboga (West African shrub)
- ibogaine (12-methoxyibogamine)
- ibogamine
- tabernanthine
- voacangine (carbomethoxy-ibogaine)
- synthetic iboga alkaloid congener 18-MC
- Vinceae
- Catharanthus
- Catharanthus roseus (a.k.a. Vinca rosea, Madagascar periwinkle)
- Rauvolfia
- Rauvolfia biauriculata (a.k.a. Rauwolfia biauriculata)
- Rauvolfia serpentina (a.k.a. Rauwolfia serpentina or devilpepper or serpentwood)
- Vinca
- Vinca difformis
- Vinca minor (a.k.a. running-myrtle)
- Loganiaceae
- Spigelia
- Spigelia anthelmia (a.k.a. pink root of Demerara)
- Strychnos
- Strychnois ignatii
- Strychnos nux-vomica (dog or quaker button / nux vomica) : East Indies
- Strychnos toxifera
- Rubiaceae
- Cinchonoideae
- Cinchoneae
- Cinchona [named from a countess of Chinchon] : a genus of South American trees, the source of the medicinal dried bark called calisaya bark, cinchona bark, Jesuit's bark, Peruvian, or Cardinal's bark, and quinquina. It was once widely used as an antimalarial but has been largely replaced by its alkaloids. Called also .
- Cinchona pitayensis
- Cinchona pubescens
- Cinchona succirubra Pavon et Klotzsch and its hybrids (red cinchona)
- Cinchona calisaya Weddell
- Cinchona ledgeriana (Howard) Moens et Trimen and its hybrids (yellow cinchona)
- quinine and its optical isomer
- quinidine
- cinchonidine : an alkaloid of cinchona, used as an antimalarial, chiefly in the form of the sulfate salt; administered orally.
- cinchonine : an alkaloid of cinchona used as an antimalarial, chiefly in the form of the sulfate salt; administered orally.
-
cinchonism : poisoning by the injudicious use of cinchona bark or
its alkaloids, characterized by nausea, vomiting, headache,
tinnitus, deafness, symptoms of cerebral congestion, vertigo, and visual
disturbances.
- Tommaselli's disease : pyrexia and hematuria due to excessive use of quinine.
- Isertieae
- Isertia
- Guettardeae
- Naucleeae
- Adina
- Mitragyna
- Neonauclea
- Neonauclea sessifolia
- Pausinystalia
- Pausinystalia johimbe
- Sarcocephalus
- Uncaria
- Uncaria guaianensis
- Uncaria tomentosa (a.k.a. una de gato)
- pentacyclic > tetracyclic alkaloids induce NK and Th lymphocytosis
- 7 different glycosides of quinovic acid
- quinovic acid glycoside 7
- quinovic acid 3 b-O-b-D-quinovopyranoside
- quinovic acid 3 b-O-b-D-fucopyranosyl-(27----1)-b-D-glucopyranosylester
- quinovic acid 3 b-O-[b-D-glucopyranosyl-(1----3)-b-D-fucopyranosyl]-(27----1)- b-D-glucopyranosylester
- quinovic acid 3 b-O-b-D-fucopyranoside
- Ixoroideae
- Coffeeae
- Coffea spp. (a.k.a. coffee)
- Coffea arabica (coffee) : low content of ...
- Coffea canephora (a.k.a. Coffea robusta) : high content of ...
- Rubioideae
- Psychotrieae
- Psychotria
- Psychotria ipecacuanha (a.k.a. Cephaelis ipecacuanha, ipecac, "Brazil root")
- cephaeline
- isocephaeline
- neocephaeline
- 7'-O-demethylcephaeline
- 10-O-demethylcephaeline
- 2'-N-(1"-deoxy-1"-b-D-fructopyranosyl)cephaeline
- 2'-N-(1"-deoxy-1"-b-D-fructopyranosyl)neocephaeline
- protoemetine
- emetine
- 9-demethylprotoemetinol
- psychotrine
- Psychotria viridis (Chacruna)
- Spermacoceae
- Bouvardia
- Bouvardia ternifolia
- Lamiales
- Lamiaceae
- Coleus
- Coleus barbatus (a.k.a. Coleus forskohlii)
- Nepetoideae
- Lavanduleae
- Lavandula
- Lavandula angustifolia (a.k.a. lavender)
- Lavandula angustifolia subsp. angustifolia
- Lavandula latifolia
- Mentheae
- Mentha
- Mentha x piperita (a.k.a. Mentha piperita, Mentha aquatica x Mentha spicata, peppermint)
- Mentha spicata (a.k.a spearmint)
- Mentha cardiaca
- Nepeta
- Nepeta cataria (a.k.a. catnip, catmint)
- Origanum
- Origanum vulgare (a.k.a. oregano)
- Rosmarinus
- Rosmarinus officinalis (a.k.a. rosemary)
- Salvia
- Salvia divinorum (diviner's sage)
- Salvia miltiorrhiza (a.k.a. danshen)
- Salvia officinalis
- Salvia splendens (a.k.a. bonfire salvia, scarlet sage)
- Thymus
- Thymus vulgaris (a.k.a. thyme)
- Ocimeae; Ocimum;
- Ocimum basilicum (a.k.a. sweet basil)
- Ocimum sanctu (Indian holy basil)
- Scutellarioideae
- Scutellaria
- Scutellaria baicalensis (a.k.a. huangqin, Baikal skullcap)
- baicalein
- Scutellaria barbata (a.k.a. banzhilian)
- Teucrioideae
- Teucrium
- Teucrium chamaedrys
- Oleaceae
- Ligustrum (privets)
- Ligustrum lucidum (glossy privet)
- iso-8-epikingiside
- 8-demethyl-7-ketologanin
- 8-epikingiside
- kingiside
- ligustroside
- 10-hydroxyligustroside
- ligustaloside A
- ligustaloside B
- Pedaliaceae
- Sesamum
- Sesamum indicum (a.k.a. sesame, Sesamum orientale, beniseed, gingelly)
- Veronicaceae
- Digitalis (a.k.a. foxgloves)
- Digitalis lanata
- Digitalis purpurea (a.k.a. common foxglove)
- Solanales
- Convolvulaceae
- Argyreia
- Argyreia nervosa (a.k.a. Hawaiian baby woodrose)
- Ipomoea spp.
- Ipomoea violacea (morning glory)
- Turbina
- Turbina corymbosa (ololiuqui, Rivea corymbosa, Christmasvine)
- Solanaceae
- Atropa
- Atropa belladonna (a.k.a. belladonna)
- Capsicum spp. (a.k.a. peppers)
- Datura
- Datura fastuosa
- Datura metel
- Datura stramonium (a.k.a. jimsonweed ("Jamestown weed", in reference to the fact that in 1676 cooks mistakenly added this species to salads eaten by English soldiers at Jamestown, Virginia), common thorn apple) : the most common species of Datura
- Hyoscyamus
- Hyoscyamus niger (a.k.a. henbane)
- Nicotiana spp. (a.k.a. tobaccos) :
- nicotine (1-methyl-2-(3-pyridyl)pyrolidine) is a Lys derivative, a very poisonous, colorless, soluble fluid alkaloid with a pyridine-like odor and a burning taste, obtained from tobacco or produced synthetically. It is used in veterinary medicine as an external parasiticide, and in pharmacological and physiological studies for its neurological effects
- nicotine polacrilex : nicotine bound to an ion exchange resin; used in nicotine chewing gum as an aid to smoking cessation.
- nicotine sulfate : the sulfate salt of nicotine, formerly a component of veterinary vermifuges; it can cause poisoning in lambs and calves
-
tabacosis (a pneumoconiosis)
-
stomatitis
nicotina / smoker's palate or patches
-
respiratory
bronchiolitis
-
respiratory
bronchiolitis–associated interstitial lung disease
-
centriacinar
or postbronchitic emphysema
- tobacco poisoning / tabagism / tobaccoism : poisoning by tobacco, usually taking the form of ...
- nicotine poisoning / nicotinism : poisoning by ingestion of excessive amounts of nicotine, usually seen in children who eat cigarettes or in workers who handle wet tobacco leaves; symptoms include stimulation followed by depression of the CNS and ANS and occasionally death due to respiratory paralysis
-
green tobacco sickness (GTS) : a transient, recurrent form of nicotine
poisoning seen in tobacco harvesters, caused by absorption of dissolved
nicotine from wet tobacco leaves through unprotected skin; symptoms include
headache,
dizziness, vomiting, and prostration.
- mall doses: respiratory stimulation, nausea and vomiting, dizziness, headache, diarrhea, tachycardia, elevation of blood pressure, sweating and salivation. The patient will gradually recover, after a period of weakness
- large doses: burning sensation of the mouth, throat, stomach, followed immediately by the above symptoms. Patient may progress to prostration, convulsions, bradycardia, arrhythmia and finally coma. Death may occur within 5 minutes to 4 hoursref.
- reduces fertility, compromises the length of gestation and infant birthweight.
- tobacco smoke contains > 60 carcinogens, including the following classes of compoundsref1, ref2 :
- 1,3-butadiene (BDE) appears to present the greatest cancer risk. However, BDE is not a group 1 IARC carcinogen, and it is possible that the potency factor calculated for BDE by the Cal/EPA, which is based on lung tumours in mice, assumes a relation to human cancer risk that is inappropriate. For example, recent studies indicate that the metabolic pathway of BDE leading to genotoxic products is considerably less prominent in humans than in ratsref. However, the CPF for BDE has recently been reviewed by Cal/EPAref with the result a lowering of the potency factor from 3.4 (mg/kg/day)-1 to 0.6 (mg/kg/day)-1. Therefore the CPF for BDE is based on the best current scientific assessment. On the other hand, even if it were determined that the CPF for BDE is overly conservative and should be reduced by, for example, an order of magnitude, BDE would still be a major carcinogen in cigarette smoke. The contributions of volatile organic compounds to overall cancer risk index are dominant even in the absence of BDE. Clearly, if a harm reduction effort for cigarette smoke were to be initiated, a focus should be on the reduction of volatile organic compounds. As these compounds are not normally included in the estimate of "tar", which is total particulate matter minus nicotine, the use of tar as a surrogate for carcinogenicity of cigarette smoke may be inappropriate. This would be particularly true if some modification to cigarettes increased the BDE concentration while leaving other constituents unchanged. Some important chemicals in the gaseous phase of tobacco smoke, such as benzene, are correlated with the amount of tarref.
- N-nitrosamines : the estimated contribution to cancer risk from nitrosamines is smaller than that for aldehydes and small organics, but is not negligible. There are 4 tobacco specific nitrosamines (TSNAs) that are reported in the literatureref:
- N-nitrosoanabasine (NAB)
- N-nitrosoanatabine (NAT)
- 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NKK) is formed during the curing and processing of tobacco by nitrosation of nicotine. Nicotine and NNK have structural similarities, and they are both metabolized extensively by lung tissue via several steps known to require oxidative enzyme systems, such as cytochrome P450. Nicotine can potentially interfere with the carcinogenicity of NNK by competition for enzyme systems essential for the metabolic activation of the nitrosamine and by competition as ligand for nicotinic cholinergic receptorsref
- N-nitrosonornicotine (NNN)
- N-nitrosodiethylamine (NDEA)
- N-nitrosodimethylamine (NDMA)
- N-nitrosopyrrolidine (NP)
- N-nitroso-N-dibutylamine
- N-nitrosoethyl-methylamine
- N-nitrosodiethanolamine
- N-nitrosopiperidine
- volatile products of combustion also figure prominently in the potential risk to the cardiovascular system
-
polynuclear
aromatic hydrocarbons (PAH)
: although benzo(a)pyrene and other carcinogenic
PAHs are widely cited as important carcinogens in cigarette smoke, this
analysis surprisingly showed that the potential risks from these compounds
were low in comparison to many other compounds in smoke. Even if the CRIs
from all the PAHs suspected to be human carcinogens were combined in mainstream
smoke, the risk index would give a ranking that is still lower than the
16th highest ranked compound, NDEA. Therefore it appears that PAH’s may
be receiving a greater level of attention than they actually deserve in
relation to the other chemical constituents in tobacco smoke.
- benzo(a)pyrene
- dibenzo(a,i)pyrene
- benzo(j)fluoranthene
- benz(a)anthracene
- dibenz(a,h)anthracene
- 2-aminonaphthalene
- benzo(b)fluoranthene
- indeno(1,2,3-c,d)pyrene
- N-nitroso-N-propylamine
- benz(k)fluoranthene
- 7H-dibenzo(c,g)-carbazole
- 5-methylchrysene
- chrysene
- dibenz(a,j)acridine
- dibenz(a,h)acridine
- aromatic amines
- acrylonitrile
- acetaldehyde
- acetamide
- hydrazine
- DDT
- urethane
- vinyl chloride
- 4-aminobiphenyl
- metals
-
arsenic
- beryllium
- cadmium
- chromium (hexavalent)
- lead
- nickel
-
benzene
-
2,3,7,8-tetrachlorodibenzo-p-dioxin
(TCDD)
-
lung cancer
: Sir Richard Doll, the British epidemiologist whose research first established
the link between smoking and lung cancer, died aged 92 in 2005. Doll warned
in a 1950 study, co-written with Sir Austin Bradford Hill, that smoking
was a major cause of lung cancer. Their early results showed that smokers
were much more likely to die of lung cancer than non-smokers, while longer-term
results linked cigarettes to heart disease and other illnesses. In 1954,
80% of British adults smoked, compared to about 25% now.
-
oral cavity cancers
-
highest risks for follicular
lymphoma
in blond (OR = 2.1, 95% CI 1.4-3.2) and mixed (OR = 1.8, 95% CI 1.1-3.0)
tobacco smokers and for large
cell lymphoma
within the other WF group (OR = 1.6, 95% CI 1.1-2.4) only for blond tobaccoref
- the respiratory irritation NCRI of cigarette smoke appears to be driven by acrolein, acetaldehyde, and formaldehyde. A substantial amount of human exposure data have been factored into the RELs for these compounds, and so the degree of uncertainty about the RELs is minimal. It is implicit, but not firmly established, that exposure to atmospheres that exceed the RELs for chronic respiratory irritation and inflammation has a direct relation to chronic respiratory disease (asthma, or other chronic lung diseases, including emphysema).
- the NCRI estimates for cardiovascular toxicity rely more heavily upon extrapolations from primate and other lab animal data, and the compounds involved have a variety of toxicological mechanisms that may not be additive. Therefore these calculations involve a greater degree of uncertainty. However, regardless of the issue of additivity of mechanisms, hydrogen cyanide and arsenic exposures alone after only a single cigarette over a chronic period are expected to result in potential cardiovascular toxicity. The NCRI approach unfortunately does not allow for an estimation to be made of the number of individuals likely to develop heart disease. It should be emphasised that considerably greater amount of information exists on dose-response relations of carcinogens and respiratory toxicants than with cardiovascular toxicants, and this is related to the degree of confidence one has in the three types of hazard ranking.
- nicotine dependence : given the pattern of nicotine absorption described above there can be no doubt that snus is dependence forming in much the same way as other forms of tobacco consumption. There is some evidence that the dependence potential of nicotine and other psychoactive drugs is related to their speed of delivery to the brain23,25 and so one would expect snus and other non-inhaled forms of nicotine delivery to be proportionately less addictive than inhaled tobacco smoke. However, there is clear evidence that users of products with snus-like nicotine delivery profiles develop cravings and nicotine withdrawal symptoms when attempting to abstain, and find it difficult to quitref1, ref2. While snus probably does not produce stronger nicotine dependence than smoking, it has just minimal, if any, advantages over cigarettes or other smokeless nicotine delivery products in terms of its lower potential to induce dependence. In fact, its high nicotine delivery and hence dependence potential (relative to most other non-smoked delivery modalities) may be a critical factor enabling it to compete with the more rapidly absorbed nicotine from smoked tobacco. One of the biggest concerns about the use of smokeless tobacco stems from the relatively large body of evidence from a number of countries showing that oral tobacco use can cause cancer of the mouth, head, and neck. With regards to its use in India, the 2001 US Institute of Medicine (IOM) report stated that, "A large number of studies in India, including cohort, case-control, and intervention studies, support an association between oral cancer and smokeless tobacco, and these studies are consistent, strong, coherent and temporally plausible". The IOM report stated that toombak users in Sudan also have a much higher relative risk (RR) of oral cancer than non-users and that "In spite of conflicting US data, it can be concluded that snuff use in the United States also increases the risk of oropharyngeal cancers". In contrast, there is consistent evidence from two case–control studies in Sweden showing no increased risk of cancer of the head, neck, or mouth among snus users. Schildt and colleaguesref investigated whether snus leads to increased risk of oral cancer by comparing various risk factors in 410 cases of oral cancer and 410 matched controls identified during the period 1980–89. 96% of the identified cases and 91% of identified controls participated in the study (leaving full data from 354 matched pairs) and 20% of the overall sample were current or ex snus users. Univariate analyses found significant increased risk of oral cancer as a result of smoking (odds ratio (OR) 1.8 for active smokers), and alcohol (OR 1.9 for beer drinkers) but no increased risk for active snus use (OR 0.7, 95% confidence interval (CI) 0.4 to 1.1). The authors concluded:"Our results do not support any association between use of oral snuff and oral cancer." Lewin and colleaguesref conducted a similarly designed study, identifying cases of head and neck cancer in 2 regions of Sweden between 1988 and 1991 and matched controls. Interviews were conducted with high proportions of identified cases (90%) and controls (85%). This study found significantly increased risks of head and neck cancers associated with alcohol use and smoking, but no increased risk associated with former or current snus use. The RR for head and neck cancer among snus users as compared with non-snus users, after adjusting for age, region, alcohol, and smoking was 1.0 (95% CI 0.6 to 1.6). Similarly there were no significant relations between duration of snus use or lifetime consumption and head/neck cancer. A recent systematic review of the health effects of smokeless tobacco concluded:"Chewing betel quid and tobacco is associated with a substantial risk of oral cancers in India. Most recent studies from the US and Scandinavia are not statistically significant, but moderate positive associations cannot be ruled out due to lack of statistical power."ref Snus causes a number of non-malignant oral diseases, including oral lesions and dental cariesref. However, it appears as though the lesions produced by snus are reversible and disappear if snus use ceases
- other cancers : Ye and colleagues32 conducted a case control study (504 cases and 1164 controls) examining the effects of smoking, alcohol, and snus use on gastric cancer in Sweden. They found a significant dose and duration related increase in gastric cancer risk with smoking, but no effect of snus or alcohol. They concluded that "smoking, but not the oral use of tobacco in the form of moist snuff, is positively associated with risk of gastric cancer". Lagergen et alref conducted a case–control study designed to test the association between smoking, snus, and alcohol use, and cancer of the oesophagus and gastric cardia in Sweden. Combined smoking and alcohol use was strongly associated with oesophageal squamous cell carcinoma (OSCC)(OR 23.1 for heavy users compared with never users), but snus use was not significantly associated with any of the cancer sites under study in multivariate analyses. There was some indication of a possible link between snus use and OSCC in that the odds ratio was 2.0 for use for over 25 years versus never snus use, although because of the relatively small size of this sub-sample (n = 14 cases) this was not significant (95% CI 0.9 to 4.1). The authors concluded:"we found no statistically significant association between snuff dipping and risk of any of the studied tumors." It remains possible, but unlikely, that a carcinogenic effect of snus only emerges after very long term use. Bolinder and colleaguesref found a non-significant RR of death from cancer of 1.1 for snus users compared with never tobacco users (95% CI 0.9 to 1.4) in a prospective study of Swedish construction workers that included a relatively large sample, many of whom had used snus for over 40 years. The RR for cancer death was 1.0 (compared with non-tobacco users) for the 1734 snus users aged 55–65 years, most of whom would presumably have used snus for over 35 years. However, this study found significantly increased all cause mortality in snus users compared with never tobacco users, largely from elevated cardiovascular mortality. The RR for lung cancer among snus users compared with never tobacco users was 0.8 among men aged 55–65, whereas the RR was 30.6 (95% CI 14.6 to 64.1) for smokers of > 15 cigarettes per day (again compared with never tobacco users). Overall, the results of the five large studies examining snus in relation to cancer are consistent in finding no increased cancer risk among snus users. All of the Swedish studies of the relation between snus and cancer were robust enough to detect significant effects for tobacco smoking (often involving very large effect sizes), and the studies of oral cancer were also able to detect significant relations with alcohol use. The lack of relation with snus is therefore unlikely to be caused by methodological problems such as low statistical power.
- cardiovascular disease : Bolinder and colleagues conducted a series of epidemiological and clinical studiesref1, ref2, ref3, ref4, ref5 examining the effects of long term snus use on health, focusing on cardiovascular risk factors and myocardial infarction. Their first reportref focused on a cross sectional study of almost 98 000 Swedish construction workers undergoing health examinations in 1971–4, including over 5000 exclusive snus users. This study found an increased prevalence of circulatory and respiratory symptoms among snus users and heavy smokers as compared to non-tobacco users, and an increased prevalence of hypertension in snus users compared to non-tobacco users. Surprisingly this study found the lowest prevalence of hypertension among smokers of at least 15 cigarettes per day. The results were based on univariate analyses, and did not control for potential confounders other than ageref. Bolinder’s second studyref examined the relation between tobacco use and cardiovascular mortality in a larger sample (n = 135 036) of Swedish male construction workers recruited at a health examination in 1971–4 and followed up 12 years later. This study found that snus users had a significantly higher risk of dying from a cardiovascular event than never tobacco users (RR 1.4, 95% CI 1.2 to 1.6). This excess risk was comparable to that of ex-smokers who had quit in the past five years, but smaller than heavy smokers (RR 1.9 compared with never tobacco users). The analyses in this study adjusted for age and region of origin, and (for at least some analyses, although it was not always stated) also adjusted for body mass index, blood pressure, diabetes, and heart problems at the time of entering the study. Alcohol consumption and cholesterol were not measured and so could not be controlled for. Subsequent studies focused on a smaller sample of Swedish firemen (around 140, split approximately equally between snus users, smokers, and non-tobacco users). These studies found that snus use did not influence exercise capacityref, or play a major role in the atherosclerotic processref (both of which were adversely affected by smoking). However, they replicated the previous finding of higher daytime (but not night time) heart rate and blood pressure among both snus users and smokers as compared to non-tobacco usersref. Overall, these studies by Bolinder and colleagues are suggestive of an increased cardiovascular risk from snus use, that is probably mediated by nicotine’s sympathetic stimulant effects, and is of a smaller magnitude than the excess cardiovascular risks caused by smoking. It was suggested that snus’ effects on blood pressure may be related to its sodium content (1.3–3.5% sodium chloride and 1.5–3.5% sodium bicarbonate). However, two subsequent case–control studies by Huhtasaari and colleaguesref did not find a significantly increased risk of myocardial infarction among snus users as compared to non-tobacco users. Both of these studies were based on data collected in northern Sweden as part of the World Health Organization MONICA (multinational monitoring of trends and determinants in cardiovascular diseases) project. In both reports, the cases and controls were identified in the 1990s. Huhtasaari and colleagues40 found an age adjusted OR for myocardial infarction (MI) of 0.89 (95% CI 0.62 to 1.29) for snus use versus no tobacco use, whereas smoking significantly increased risk of an MI (OR 1.87, 95% CI 1.40 to 2.48). In multivariate analyses smoking remained significantly associated with MI, whereas snus use was not. Huhtasarri subsequently conducted a larger study than the one reported in 1992, and included more detailed tobacco use histories and closer matching of cases and controls (matched for sex, date of birth, and area of residence)ref. This study found (after adjustment for multiple cardiovascular risk factors) that cigarette smoking significantly increased risk of an MI (OR 3.53, 95% CI 2.48 to 5.03), whereas snus use significantly reduced the risk (OR 0.58, 95% CI 0.35 to 0.94) compared with men who never became regular tobacco users. When the analysis focused only on fatal cases, there was a tendency towards increased risk in snus users, but this was not significant (OR 1.5, 95% CI 0.45 to 5.03). There is no clear explanation for the difference in results between the Bolinderref and Huhtasaariref studies, although the different study populations, time periods covered, and outcomes measured (sudden death versus non-fatal MI) may have contributed. The similar magnitude of effect for fatal cardiovascular events found in these studies is suggestive of a slightly increased risk overall. On the other hand it remains possible that the effect of snus in the Bolinder study was caused by some unmeasured (and therefore uncontrolled) confounding factor, with dietary habits and alcohol consumption being examples of baseline variables not measured in that study. This possibility is supported by a recent report of the effects of smokeless tobacco in the USA, based on analyses of the First National Health and Nutrition Examination Survey epidemiologic followup study (NHANES-1) dataref. This study had 96% follow up of the original 14 407 participants and 98% identification of death certificates for the 4604 decedents by 1992. Male smokeless tobacco users were found to have moderately increased risks of some disorders, but all of these excess risks disappeared when variables such as race and poverty were controlled for. For example, the crude hazard ratios for male smokeless users versus non-tobacco users were 1.5 and 2.1 for circulatory and respiratory diseases before adjustment, but after adjustment for confounders these hazard ratios became 1.0 and 0.9. One potentially serious flaw with this study42 is that pipe and cigar users were included in the "non-tobacco user" comparison group, seriously undermining confidence in their conclusion that US smokeless tobacco users have similar mortality outcomes to non-tobacco users. We cite this paper as an example of the changes in outcomes that can result from controlling for baseline variables, rather than as evidence of the safety of US smokeless tobacco. Bolinder et al’s first studyref found snus users to be at excess risk of a number of respiratory symptoms. For example, the OR for "cough in the morning" for snus users versus never tobacco users was 2.1 (95% CI 1.8 to 2.4), as compared with an OR of 7.9 for smokers versus never tobacco users. It is not easy to think of a plausible mechanism whereby exclusive snus use might cause respiratory symptoms. This study excluded all those who reported mixed use of snus and cigarettes or reported being an ex-smoker (n = 59, 864 excluded). However, the increased respiratory symptoms suggest the possibility that some of those reporting exclusive snus use were actually occasional or ex-smokers. Passive smoke exposure is another possible confounding factor that could potentially contribute to these findings. This study was initially funded by a health insurance group with the purpose of examining factors affecting sick leave and disability pensions. Some participants may have under-reported their recent or ex-smoking due to their belief that it either was not worth mentioning, or out of a concern that it may somehow affect their future benefits. In reviewing the evidence from a range of clinical and experimental studies, Benowitzref concluded:"Overall, the epidemiologic and experimental data suggest that nicotine absorbed from smokeless tobacco, nicotine gum or transdermal nicotine is not a significant risk factor for accelerating coronary artery disease or causing acute cardiovascular events." This conclusion is supported by a recent case–control study that examined risk factors for stroke among Swedish menref. In multivariate analyses, controlling for other risk factors, smoking was related to increased risk of stroke (OR 1.74) whereas snus use was not (OR 0.87, 95% CI 0.41 to 1.83). Given the inconsistencies in the results of these studies, it remains possible that snus users have a slightly increased cardiovascular risk as compared to never tobacco users, even after controlling for other confounding factors. However, all of the large studies of the effects of tobacco use on cardiovascular disease in Sweden are in agreement that "the use of smokeless tobacco (with snuff being the most studied variant) involves a much lower risk for adverse cardiovascular effects than smoking does"ref.
- respiratory diseases : a Pubmed search did not identify any studies that specifically examined the effect of snus on respiratory diseases; similarly the IOM report did not address the effects of smokeless tobacco on respiratory illnesses.3 The reason for this is presumably that there is no plausible causal mechanism whereby smokeless tobacco could cause respiratory disease. A recent study of mortality in US smokeless users reported no increased risk of respiratory diseases in smokeless usersref. This contrasts heavily with the effect of continued smoking on chronic obstructive pulmonary disease, with 50% of elderly Swedish smokers developing the condition as compared with less than 20% of never smokersref.
- diabetes : Bolinder found that smokers had significantly higher fasting blood glucose values than never tobacco users whereas snus users were not significantly different from never users. Eliasson and colleagues47 found that neither smoking nor snus use was associated with changed glucose tolerance or insulin concentrations. However, a more recent study by Perssonref found an increased risk of (asymptomatic) type 2 diabetes among both heavy smokers (25+ cigarettes per day) and heavy snus users (3+ cans per week), with significant odds ratios of 2.7 and 2.6, respectively, for these two groups as compared with non-tobacco users. It should be noted that this study specifically recruited men over 35 years old, 50% of whom had a family history of diabetes. The effects of snus on risks for diabetes are unclear and it may be that any effects are restricted to heavy users and/or those with a family history of diabetes.
- pregnancy : a Pubmed search did not identify any studies that had specifically examined the effects of snus use during pregnancy. However, given that animal studies have implicated nicotine as a cause of some of the widely known adverse effects of tobacco exposure during pregnancy (on both the health of the mother and healthy development of the fetus), it follows that snus use during pregnancy is likely to incur some of the risks associated with smoking during pregnancyref. The preliminary results of one study (as yet unpublished) have been presented at a conference earlier this year. The study examined data from the Swedish Birth Register for women who delivered babies during 1999–2000. The study compared 789 snus users to 11 242 cigarette smokers and 11 500 women not using any tobacco. Smokers gave birth to babies weighing an average of 206 g (7.3 ounces) less than non-tobacco users. Snus users gave birth to babies weighing an average of 40 g (1.4 ounces) less than non-tobacco users. Snus users were also about twice as likely as non-tobacco users to deliver prematurely (perhaps partially explaining the slightly lower birth weight), and were more likely than both smokers and non-tobacco users to suffer pre-eclampsia. Clearly, the full results of this study and additional studies on this topic are required before coming to conclusions, particularly given the possibilities for confounding variables to cause small sized effects. However, given the known risks of nicotine in pregnancy, and the preliminary results of this unpublished study, it seems likely that snus use can cause adverse health effects in pregnancy and should not be promoted as safe for use in pregnancy. It would be a particular cause for concern were there to be evidence of increased snus use among women of reproductive age, without an equal or greater reduction in smoking in that group. Given that smoking during early pregnancy in Sweden has already declined from 31% in 1983 to 12% in 2000, it could be argued that the potential for snus to have a "positive" impact on smoking in pregnancy has similarly shrunk. It would seem as though Swedish women are on a positive trend towards tobacco-free pregnancies without snus, and that it would be best kept that way.
inhibitor used to treat Alzheimer's
disease=> savin oil : an acrid oil from the fresh tops, the chief constituent of which is sabinol; it has been used in folk medicine as an emmenagogue, anthelmintic, and antirheumatic, and is used in perfumery. It may cause hematuria and violent gastrointestinal irritation when administered internally; fatal poisoning has resulted from its use as an abortifacient.
=> cedar oil / cedarwood oil / oil of cedar wood : a volatile oil from the wood used as a clearing agent in microscopical techniques; the thicker fraction is used as the immersion medium with oil-immersion objectives
=> pine oil : the volatile oil obtained by steam distillation of the wood; used as a deodorant and disinfectant.
=> rectified tar oil : the volatile rectified by steam distillation; in veterinary medicine, administered internally as a stimulant expectorant and externally as an antipruritic, antiseptic, and stimulant for skin diseases. Also used as a disinfectant and deodorizer
=> taxol
=> flavonoid glycosides and terpenic lactones => increased cerebral blood flow.
Americans consumed nearly $250 million of this herbal product in 2000. The literature shows no evidence that it improves cognition, but it may decrease the risk of dementia.
=> astins : antitumour pentapeptides consisting of a 16-membered ring system containing a unique b,g-dichlorinated proline [Pro(Cl)2], other non-coded amino acid residues and a cis conformation in one of the peptide bonds
=> 6-methylapigenin, a GABAA
ligand=> camptothecin
and block Na+ flux.
=> benzoin
The beverage tea, from the top leaves, is one of the most widely used beverages in the world, second only to water.
,
and acts as an antagonist A1,
A2a,
A2b,
and A3
receptors.
=> antioxidants : green tea polyphenols (GTP) down-regulate the IGF-1
-driven
molecular pathway (including PI3K, Akt and Erk1/2) and indirectly down-regulating
plasma VEGF
in prostate tumor cells. GTP inhibited the levels of urokinase plasminogen
activator as well as MMP2
and MMP9,
cellular molecules linked to the metastasis.
has been detected where the people religiously drink the tea. Traditionally,
the Kombucha culture is considered to be holy, and whoever receives the
"mushroom" promises to treat it reverently; if they were unable to continue
caring for the culture, then they must pass it on to a caretaker so it
may continue to flourish. Anecdotally it is reported to affect a plethora
of conditions, resulting in anything from a feeling of well-being to curing
a variety of diseases. Controlled studies, such as would be required to
have it recognized as a drug, seem to be lacking.=> SL0101 inhibits RSK in breast cancer cells
=> lochnerin, an indole alkaloid
=> reserpine (Adelphan®, Barecal®, Eubamat®, Modenol®, Ondasil®, Pacyl-R®, Sedaraupin®, Serpasil®, Serpatonil®) : it impairs ACh
vesicles accumulation in presynaptic terminal=> vincristine
=>
=> toxiferines : they are N
antagonists.=> strychnine is an alkaloid extract obtained from the dried ripe seeds : it inhibits Gly receptor
; in the past strychnine has been used as an antiseptic, stomach tonic,
circulatory stimulant, CNS stimulant, and as a medication for the relief
of constipation;
The minimal oral LD50 ranges from 30 to 120 mg, but this can
be somewhat lower when given i.v. or s.c.. However, enzymes of hepatic
microsomes readily metabolize strychnine, so 2 LD50 can be given
over 24 hours and not have cumulative effects. Of course, LD50
for children may be much lower
Symptoms & signs : strychnism (strychninism is chronic strychnine poisoning) : within 15-30' (occasionally there is a delay of 1 hour if it is taken by mouth, as the time of action depends on whether the stomach is empty or full, and on the type of food that is eaten) uneasiness, restlessness, anxiety, hyperreflexia, muscle twitching, midriasis, and stiffness of the neck => increased acuity of hearing, vision, touch, taste, and smell, followed by tetanus-like tonic convulsions
of all striated muscles every 10-15', severe cyanosis (which disappears
after the attack subsides), and nausea
and vomiting.
The attacks (each lasting about 3-4') appear to be spontaneous, while at
other times they are the result of external stimuli, i.e., noises, slight
movements, or flashes of light. The patient never loses consciousness.
When the poisoning is left untreated, each attack lasts longer than the
previous one and the interval between them grows shorter. Up to 10 attacks
occur before death or recovery. This could happen from 10' to 3 hrs and
is a result of asphyxiation or inner tissue paralysis.
Laboratory examinations : identifying strychnine in the stomach contents and viscera by chemical tests
and microscopic identification of typical strychnine crystals.
Therapy : i.v. diazepam
=> gastric lavage
Strychnine produces a painful death. A dog ingesting strychnine presents with no vomiting or diarrhea. The initial clinical signs are a restless, anxious dog, that is described as *walking on egg shells* with increased respirations, not quite panting. This progress to constant panting, muscle tremors. Finally tetanic seizures or convulsions
that occur spontaneously or with touch, light, or noise stimuli. The limbs
extend, the head is
curved upwards and backwards and the lips are pulled back in what has been termed a sardonic grin. The severity and duration of convulsions are not prognostic. Death is generally from asphyxia due to prolonged paralysis of the respiratory muscles. When the dog is in seizures, the muscles of the diaphragm are paralyzed and the dog cannot breath. Death may be as sudden as 5 to 10 minutes or as long as 2 hours. Animals poisoned with strychnine can be successfully treated. If the animal was seen ingesting a known bait, and is not showing signs the veterinarian should induce emesis (vomiting). Animals showing clinical signs should have the convulsions controlled and respiratory support initiated. Pentobarbital sodium is the drug of choice, administered to effect. (Phenobarbital is not as effective due to the long period of time before it takes effect.) It may be necessary to perform gastric lavage to decrease adsorption of any
strychnine remaining in the stomach. The veterinarian should thenadminister activated charcoal. The charcoal should be removed from the stomach by sedating the animal and flushing the stomach or by administration of a saline cathartic. Forced diuresis with acidification of the urine is appropriate. An anesthetic machine may utilized to support respiration for an extended period of time, however, this removes it from use in surgeries. A respirator is better, if available. Use of central acting skeletal muscle relaxants such as glyceryl guaiacolate and/or methocarbamol are recommended, but require frequent redosing. The animal will need to have its temperature maintained by use of blankets and placed in a dark quite room. Turn the animal periodically to prevent hypostatic congestion. The continued administration of activated charcoal may prevent the convulsions which re-occur 1-3 days after apparent recovery. Strychnine is an ugly way for an animal to die, but these animals can be saved by proper and timely assistance.
=> quinoline alkaloids
Laboratory examinations
Side effects :
=> cinchoninic acid : quinoline 4-carboxylic acid, an oxidation product of cinchona alkaloids.
Laboratory examinations
Side effects :
=> cinchoninic acid : quinoline 4-carboxylic acid, an oxidation product of cinchona alkaloids.
=> yohimbine (Aphrodyne®, Dayto Himbin®, Plain Prowess®, Yocon®, Yohimes®, Procomil®, Procamil®) is an a2-AR
antagonist
)
: it acts as both a competitive inhibitor of phosphodiesterases,
SERCA, and an antagonist on GABAA,
A1,
A2a,
A2b,
and A3
receptors, leading to membrane hyperpolarization => decrease of vascular
resistances, positive inotropic effect on cardiomyocytes, and increase
of thiazide-induced
diuresis.
It easily crosses the placental barrier.
Caffeine has significant hemodynamic and humoral effects in habitual coffee drinkers that persist for many hours during the activities of everyday life. Furthermore, caffeine may exaggerate sympathetic adrenal-medullary responses to the stressful events of normal daily life. Repeated daily blood pressure elevations and increases in stress reactivity caused by caffeine consumption could contribute to an increased risk of coronary heart disease in the adult populationref. There is extensive evidence that caffeine at dietary doses increases BP. However, concern that the drug may contribute to cardiovascular disease appears to have been dampened by (1) the belief that habitual use leads to the development of tolerance, and (2) confusion regarding relevant epidemiologic findings. When considered comprehensively, findings from experimental and epidemiologic studies converge to show that BP remains reactive to the pressor effects of caffeine in the diet in persons who are regular consumers, even when daily intake is at moderately high levelsref. Overall, the impact of dietary caffeine on population BP levels is likely to be modest, probably in the region of 4/2 mm Hg. At these levels, however, population studies of BP indicate that caffeine use could account for premature deaths in the region of 14% for coronary heart disease and 20% for strokeref. No effect of coffee consumption on the risk of acute myocardial infarction (AMI)
.
Self-reported coffee consumption has no overall association with post-infarction
mortalityref.
For adolescents, especially African American adolescents, caffeine intake
may increase blood pressure and thereby increase the risk of secondary
systemic arterial hypertension.
Alternatively, caffeinated drink consumption may be a marker for dietary
and lifestyle practices that together influence blood pressureref.
A significant association was found between caffeine-related increase in
systolic blood pressure and caffeine-related increase in pain toleranceref.
Intake of caffeinated beverage (>/=180 mg caffeine) may not be recommended
for patients with normotensive glaucoma or ocular hypertensionref.
Caffeine intake is associated with a significantly lower risk for Alzheimer's
disease,
independently of other possible confounding variablesref.
Brazilian researchers bred 3,000 Ethiopian coffee plants as part of a programme to produce low-caffeine strains. They found 3 bushes, all derived from the same plant, that were virtually caffeine free, containing 15 times less stimulant than commercial strainsref. Caffeine-free coffee plants have been found before, growing wild in Madagascar. But they yield inferior beans unsuited for coffee production. The Brazilian shrubs belong to the species Coffea arabica, the most cultivated and consumed coffee in the world. Over 10% of coffee consumed worldwide is decaffeinated, so demand for a tasty, low-caffeine blend is high. Currently caffeine is stripped from coffee using costly industrial processes. Organic solvents and carbon dioxide are used to purge the caffeine from the beans, but they strip away key flavour compounds at the same time. An alternative that does not destroy so much of the taste is to sift out the caffeine with a carbon filter, but this is even more expensive. They have not been able to taste any coffee made from the plants as these will take several years to mature. Their bushes also grow around 30% more slowly than standard arabica plants, so the team hopes to crossbreed them with their caffeine-rich relatives to produce a fast-growing, caffeine-free variety. But selective breeding like this can take ten years or more, giving competitors a chance to edge in on the market. For example, a genetically modified low-caffeine coffee plant is just a few years from maturity.Naturally bred species can still contain trace amounts of the chemical. But those opposed to genetically modified foods may find the Brazilian approach worth the wait.
People who receive caffeine have significantly greater activation in parts of the prefrontal lobe, known as the anterior cingulate and the anterior cingulate gyrus. These areas are involved in 'executive memory', attention, concentration, planning and monitoring [Koppelstätter, 2005 meeting of the Radiological Society of North America].
Caffeine-dependent women with a family history of alcoholism were not able to follow their physician’s advice to reduce or eliminate caffeine consumption during pregnancy, despite their wanting to do so. This subgroup may require more intensive intervention to ensure caffeine abstinence and may be at greater risk for abuse of or dependence on other drugsref.
Web resources : Paullinia cupana (Guarana)
=> ipecac alkaloids :
=> N,N-dimethyltryptamine (DMT)
=> bouvardin
=> forskolin / coleonol / colforsin, labiate terpenoid
=> lavender oil / lavender flowers oil : a volatile oil distilled with steam from the fresh flowering tops or prepared synthetically; used as a perfume in pharmaceutical preparations
=> oil of spike : a volatile oil used in perfumery, and formerly in home remedies as an emmenagogue and abortive
=> peppermint oil : the volatile oil distilled from the fresh above-ground parts of the flowering plant, used as a flavor in pharmaceutical preparations, and as a gastric stimulant and carminative
=> spearmint oil : the volatile oil distilled with steam from the fresh overground parts, yielding at least 55% by volume of carvone; used as a flavor for pharmaceutical preparations
=> nepetalactone
=> used against Listeria monocytogenes
=> rosemary oil : the volatile oil distilled with steam from the fresh flowering tops, used as a flavoring or perfuming agent
=> rosmarinic acid (RosA) induces p56lck-dependent apoptosis in Jurkat and peripheral T cells via mitochondrial pathway independent from Fas/Fas ligand interaction
=> salvinorin A : ?
=> salvinorin B
=> anticoagulants
=> salviarin
=> splendidin
=> thyme oil : the volatile oil distilled from the flowering plant; used as a flavoring agent for drugs, and has been used as a rubefacient, expectorant, counterirritant, antiseptic, and carminative
=> orientin (Ot)
=> vicenin (Vc), 2 water-soluble flavonoids isolated from the leaves that have shown significant protection against radiation lethality and chromosomal aberrations in vivoref.
=> flavonoids
=> hepatotoxic
=> oleanolic and ursolic acids
=> nuezhenide
=> nuezhengalaside
=> isonuezhenide
=> neonuezhenide
=> specnuezhenide
=> salidroside (p-hydroxyphenethyl-b-D-glucoside)
=> lucidumoside A
=> lucidumoside B
=> lucidumoside C
=> lucidumoside D
=> oleoside dimethyl ester
=> oleuropein
=> iridoid glucosides
=> sesame oil : the refined fixed oil obtained from the seed; it is used as a solvent and oleaginous vehicle for drugs, and has been used internally as a laxative and externally as a skin softener
=> lanatoside A - Glc => acetyldigitoxin - acetyl => digitoxin
=> lanatoside B -Glc => acetylgitoxin - acetyl => gitoxin
=> lanatoside C - Glc => acetyldigoxin - acetyl => digoxin
They all bind to a-subunit and inhibit 3 Na+ / 2 K+ ATPase
=> purpurea glycoside A - Glc => digitoxin
=> purpurea glycoside B - Glc => gitoxin
=> formyl-purpurea glycoside - Glc => formyl-gitoxin
They all bind to a-subunit and inhibit 3 Na+ / 2 K+ ATPase
=> atropine / d,l-hysocyamine / dimethylscopolamine (Atropisol®, Atropine-Care®, Isopto Atropine®)
Laboratory examinations
=>scopolamine / l-hyoscine (Isopto Hyoscine®, Transderm-Scop®)
=> hot chili peppers, whose main pungent ingredient is capsaicin : it excites peripheral nerve endings and activates vanilloid receptor 1 (VR1)
.
Oleoresin
capsicum (OC) is used even in self-defence sprays together with o-chlorobenzylidene
malononitrile and 2-chloroacetophene.
=> scopolamine / hyoscine
=> atropine / d,l-hysocyamine / dimethylscopolamine
=> scopolamine / hyoscine
In Bangladesh, there is a tendency to use powder of Datura spp. (most probably D. fastuosa) or some species of Oleander seed in food items, drink or cigarettes by miscreants and offering them to unsuspecting people. Because of the action of Datura or Oleander seed, people become unconscious and then the criminals grab their valuable items.
=> atropine / d,l-hysocyamine / dimethylscopolamine
=> scopolamine / l-hyoscine
Epidemiology : there are nearly 1.1 billion users of nicotine and tobacco products worldwide : 80% reside in low-income and middle-income countries. Though in the USA there has been a substantial decline in cigarette smoking since 1964, when the Surgeon General's report first reviewed smoking, smoking remains widespread in the USA (about 23% of the population in 2001). Tobacco use through cigarette smoking is the leading preventable cause of death in the world and kills nearly 4 million people annually. 30% of all deaths in smokers in the 35 to 69 years age range are attributed to chronic cigarette smoking; smokers dying in this age cohort lose an average of 23 years of life. In UK the percentage of people smoking fell from 45% in 1974 to 26% in 2003-4. Smoking remains most common among manual workers (35% for men and 31% for women) and is lowest among people in managerial and professional jobs (20% for men and 17% for women)ref. Cigarettes are probably the single most significant source of toxic chemical exposure and chemically mediated illness in humans. The WHO forecasts cigarettes will kill nearly 10 million people per year globally by the year 2020. Newly emerging tobacco products, notably products that claim to heat, rather than burn, tobacco come with claims of reduced toxicant yields and reduced harmfulness as they are test marketed internationallyref. At the same time, governments are starting to require smoke constituents to be analysed and reportedref. It is unlikely that a "safe cigarette" could ever be developed, as combustion products in smoke are inherently potentially harmful. Nevertheless, it may be possible to reduce some of the toxic potency of cigarettes if the most significant causative agents of disease can be identified and reduced or eliminated. However, it is important that such a strategy does not give the public the false impression that cigarette smoking has become a safe practice. Such a perception could counteract any public health gains made by the reduction of the toxicity of tobacco smoke. Ideally, policies to do with prevention of smoking would concentrate on preventing people from starting to smoke or assisting them to stop smoking entirely. However, such policies have been only partially successful, with the worldwide number of smoking related deaths at around 4 million annually and climbing.
Pathogenesis : cigarette smoke is a complex mix of some 4,000 chemicals. Many of these are harmful to hum health :
It is an agonist of N
receptor and a tumor promoter (activates
PKB / Akt pathway)
=> nornicotine
=> neonicotine / anabasine
They all are used as botanical insecticides
Most of them are believed to cause smoking-associated cancers : tobacco smoke causes 63% of cancer deaths among African-American men in the USA The smoke-related cancer death burden for African-American men is highest in the South at 67%, with the lowest burden, 43%, in the Northeast. The percentage is 60 in the West and 63 in the Midwestref.
on bronchial epithelial and endothelial cells.
The results of a 50 year analysis on 34,439 male British doctors who first reported their smoking habits at the end of 1951 show that lung cancer was the malignancy responsible for the largest number of deaths related to smoking. The number of deaths per year per 100,000 men who were heavy smokers (25 or more cigarettes a day) was 25 times that among their colleagues who never smoked (415.2 versus 16.9). For lung cancer
,
like a number of other cancers, there was a progressive increase in risk
with the number of cigarettes smoked. Mortality from lung cancer was 3
times higher among heavy smokers than among light smokers (< 15 cigarettes
a day) (130.6 deaths per year per 100,000 men). Similar differences in
mortality between heavy smokers and men who never smoked were shown for
esophageal
cancers
(50.0 versus 5.7 deaths per year per 100,000 men), bladder
cancers
(51.4 versus 13.7), the laryngeal
cancers
(17.3 versus 0), and the pancreatic
cancers
(52.9 versus 20.6). 2 types of cancer—rhinopharyngeal
cancers
and nasal cancers-
contributed only small numbers of cases, but the evidence, say the authors,
indicates a positive relation with smoking. No firm link was found for
prostate
cancers:
data, now based on nearly 900 deaths, show some increasing risk with increasing
numbers of cigarettes smoked per day, but only among smokers; there is
no appreciable difference between non-smokers and continuing smokers and
the lowest risk is recorded in ex-smokers. They tend, therefore, to support
the idea that smoking is unrelated to the disease. Some evidence is shown
that rectal cancers,
but not colon cancers,
is related to smokingref.
Compared with those who had never smoked, those who smoked 1-5 cigarettes a day were almost 3 times as likely to die of coronary artery disease
.
While there was little difference in the risk of dying from any type of
cancer, this was not the case for lung
cancer.
Men who were light smokers were almost 3 times as likely to be killed by
lung cancer. And women were almost 5 times as likely to die of the disease
as their non-smoking peers. Light smokers also had significantly higher
death rates from all causes - 1.5 times - than those who had never smoked,
with the death rates corresponding to the number of cigarettes smoked every
day. As the light smokers had smoked for fewer years than the heavy smokers,
the researchers analysed the projected impact of smoking at this level
for 5 years. This indicated that the risk of death from coronary artery
disease would have been 7% higher, and the risk of lung cancer would have
been 47% higher in women. (Tobacco Control, Sep 2005)Since 1950, the makeup of cigarettes and the composition of cigarette smoke have gradually changedref. In the USA, the sales-weighted average "tar" and nicotine yields have declined from a high of 38 mg "tar" and 2.7 mg nicotine in 1954 to 12 mg and 0.95 mg in 1992, respectively. In the United Kingdom, the decline was from about 32 mg "tar" and 2.2 mg nicotine to less than 12 mg "tar" and 1.0 mg nicotine per cigarette. During the same time, other smoke constituents changed correspondingly. These reductions of smoke yields were primarily achieved by the introduction of filter tips, with and without perforation, selection of tobacco types and varieties, utilization of highly porous cigarette paper, and incorporation into the tobacco blend of reconstituted tobacco, opened and cut ribs, and "expanded tobacco". In most countries where tobacco blends with air-cured (burley) tobacco are used, the nitrate content of the cigarette tobacco increased. In the USA nitrate levels in cigarette tobacco rose from 0.3-0.5% to 0.6-1.35%, thereby enhancing the combustion of the tobacco. The tobacco industry added certain substances to cigarettes to make them more palatable to children and young people. Menthol, for example, was added to most cigarettes (not just to those described as mentholated) because inhaling menthol has an anaesthetic effect, allowing first time smokers, who were often children, to take deep puffs. Sugar and aromatics were also added to make cigarettes taste better. The addictive potential was also increased by manipulation of filters and cigarette sheaths, which meant that smokers took deeper breaths and therefore had greater exposure to carcinogenic and other toxic substances. Additives such as ammonia, urea, menthol, sugar, and cocoa had been blended with raw tobacco over the last 5 decades. The formula for tobacco addiction was to take nicotine, decrease acidity, and add aromatic substances which enable smokers to take deep breaths. According to legal regulations cigarettes are allowed to contain up to 600 different substances and chemically undefined mixtures which make up 10% of the total weight of one cigarette : criticised additives had been legally permitted since 1964ref1, ref2. Scientists at its GenApps Inc. laboratories of U.S. Smokeless Tobacco Company (USSTC) discovered nicotine demethylase, the enzyme that facilitates the conversion of nicotine into nornicotine. Nornicotine is known to be the precursor to NNN : the discovery holds the promise for commercial production of low-nitrosamine tobacco with significantly reduced NNN levels within the next decade.
beedis : tobacco rolled in Diospyus melanoxylon leaf
In recent times the tobacco industry has been active in developing and marketing new products that might be perceived as less harmful to health than typical cigarettes. At the same time, there has been an increasingly vigorous debate within the public health community over the most appropriate response to the new products being developed by the industryref1, ref2. In this debate, public health advocates have been mindful of the historical precedents set by previous tobacco industry attempts to introduce new product lines that have been perceived as less harmful. It is now clear that so called "light" cigarettes were widely believed to be less harmful (and continue to be by the majority of consumers) but in fact are no less deadly than standard cigarettes. The introduction and marketing of these products may well have had a serious adverse effect on public health by duping hundreds of millions of smokers into the belief that they could continue to smoke at reduced risk. In the current debate over tobacco harm reduction, some have cited the "Swedish experience" as an example of tobacco product switching that may have had a positive effect on smoking and public healthref. "Snus" is the name given to the form of smokeless snuff tobacco commonly used in Sweden. It is a moist, ground oral tobacco product that is typically placed behind the upper lip, either as loose ground tobacco or contained in sachets appearing like small teabags. The snus is typically held in the mouth (without chewing) for approximately 30 minutes before it is discarded. Snus both contains and delivers a number of harmful substances, including cancer-causing tobacco specific nitrosamines (TSNAs). It has become clear that different selection and curing methods can affect the levels of nitrites and hence TSNAs present in the raw tobacco before processing. Over recent decades snus manufacturers have selected tobacco blends that have been air and sun cured (dried), while US moist snuff products tend to include blends high in fire cured tobacco. After curing, raw cured tobacco is cut into small strips, dried, ground, and sifted before processing. In Sweden, by tradition, snus production has included a process in which the tobacco is heat treated with steam for 24–36 hours (reaching temperatures of approximately 100°C). Ingredients added are: 45–60% water, 1.5–3.5% sodium chloride, 1.5–3.5% humectants, 1.2–3.5% sodium bicarbonate, and less than 1% flavouring. It is claimed that the heating process kills bacteria, producing a relatively sterile product. The product is then packaged in cans and refrigerated during storage. In Sweden the product is also kept in refrigerators by the retailers. One study examined levels of carcinogenic TSNAs in snus kept at temperatures ranging from -20°C to +23°C for 20 weeksref. This exposure to a variety of temperatures over time did not produce a significant increase in concentrations of TSNAs, suggesting that the exposure to heat during manufacturing may itself have prevented microbial activation of nitritesref. This manufacturing process contrasts with that traditionally used in the USA, in which the product is fermented (rather than being subject to high temperatures), allowing the continued formation of TSNAs. In addition, North American smokeless tobacco is not typically stored in refrigerators. One study found that nitrite and TSNA levels increased significantly in US snuff stored at 37°C for 4 weeks. Although different products vary in their pH levels, snus typically has a pH in the range 7.8–8.5ref1, ref2. This is important because only nicotine in the free-base form is rapidly absorbed through the mucosal membrane, and the proportion of free-base nicotine available from tobacco is determined by the pH level. For example Brunnemann and Hoffmann compared two brands and found that one brand with a pH of 5.84 had only 1% of the nicotine in the free-base form and another brand with a pH of 7.99 had 59% of the nicotine available in free-base form for absorptionref. Another study found that a leading Swedish snus brand had a higher pH (and therefore probably more efficient nicotine delivery) than 5 comparison brands of US smokeless tobaccoref.13 Possibly as a result of the differences in manufacturing and storing procedures, snus has been claimed to contain lower levels of some harmful substances than many of the brands available in North America and notably lower levels than exist in the smokeless tobacco used in the Sudan and India.10Table 1 below summarises data from 5 studiesref1, ref2, ref3, ref4 of TSNA levels in various samples of different brands marketed in different countries. The total TSNA concentration varied greatly among the US brands from 4.1 to 128 (µg/g dry tobacco). There is little evidence to support claims that TSNA levels have consistently dropped over the past decade in North American snuff (for example, Copenhagen brand in 1994 had a measured TSNA level of 17.2 and in 2000 it was 41.1). Snus brands selected in Sweden from 1990, 1991, and 2000 have generally been lower and have varied from 9.2 to 11.2 µg/g in the 3 samples in 1990–91 and 2.8 µg/g in 2000. Brunnemann and Hoffmann13 also examined the effects of storage for 6 months at room temperature and found that in two leading US brands, the TSNA levels increased by between 30–130% whereas in the snus brand there was no increase. More recently the manufacturer of snus has created and publicised a quality standard, the Gothiatek standard, for its snus products that includes maximum permissible limits for "undesirable substances". It is unclear if all Swedish Match smokeless tobacco products produced in Sweden and abroad adhere to the Gothiatek standard. Many of the smokeless tobacco users participating in the older epidemiological studies discussed below may have been exposed to products delivering higher quantities of harmful substances than current versions of these products