Ageing, arterial blood pressure, body mass index, and diet.

For three decades we followed up for longevity indicators, including diet, arterial blood pressure, and body mass index 379 mobile, long-living persons from Croatia, now aged 70 to 92 years, of whom 167 men aged (78.6 ± 4.0) years and 212 women aged (77.9 ± 4.1) years. One hundred and ninety-five were from the continental and 184 from the coastal Croatia. The participants were examined in 1972, 1982, and again in 2006/7. Changes in body mass index (BMI), arterial blood pressure (ABP), and in answers to our Food Frequency Questionnaire about dietary habits were analysed using log-linear models. Over the last 24 years of aging (age 55 to 78 years) the subjects showed a statistically significant decrease in body mass and height and a significant increase in the systolic blood pressure. Diastolic blood pressure and BMI showed no significant changes over this period. Consumption of preserved and fresh meat, bread, and starch (potato, pastry and rice) dropped significantly with age, while the consumption of fish, fresh and cooked vegetables, fruit, and dairy products significantly increased. These dietary changes were not associated with changes in the systolic and diastolic ABP. About 80 % were overweight (BMI >25 kg m(-2)) throughout the follow-up, even though their body mass dropped significantly after the age of 55. However, their survival suggests that BMI may not be the best indicator of longevity or healthy aging.

Pyroglyphid mites as a source of work-related allergens.

Pyroglyphid mites are primarily associated with allergen exposure at home; hence the name house dust mites. However, we have found numerous studies reporting pyroglyhid mite levels in public and occupational settings. This review presents the findings of house dust mite allergens (family Pyroglyphidae, species Dermatophagoides) as potential work-related risk factors and proposes occupations at risk of house dust mite-related diseases. Pyroglyphid mites or their allergens are found in various workplaces, but clinically relevant exposures have been observed in hotels, cinemas, schools, day-care centres, libraries, public transportation (buses, trains, taxies, and airplanes), fishing-boats, submarines, poultry farms, and churches. Here we propose a classification of occupational risk as low (occasional exposure to mite allergen levels up to 2 µg g(-1)), moderate (exposure between 2 µg g(-1) and 10 µg g(-1)), and high (exposure >10 µg g(-1)). The classification of risk should include factors relevant for indoor mite population (climate, building characteristics, and cleaning schedule). To avoid development or aggravation of allergies associated with exposure to house dust mites at work, occupational physicians should assess exposure risk at work, propose proper protection, provide vocational guidance to persons at risk and conduct pre-employment and periodic examinations to diagnose new allergy cases. Protection at work should aim to control dust mite levels at work. Measures may include proper interior design and regular cleaning and building maintenance.

Prostate cancer in elderly Croatian men: 5-HT genetic polymorphisms and the influence of androgen deprivation therapy on osteopenia--a pilot study.

BACKGROUND: The aim of this study was to determine the relationship between body mass index, biochemical parameters, and 5-hydroxytryptamine (5-HT) genetic polymorphisms and prostate dysfunction in an elderly general male population. RESULTS: One hundred and seventeen elderly male subjects [60 men without symptoms of prostate hyperplasia, 42 men with untreated benign prostatic hyperplasia (BPH), and 15 men with prostate cancer (PCa)] treated with finasteride or flutamide were included. Multiple comparisons showed significant difference in age, T-score, concentration of phosphorus, calcium, C-reactive protein, and prostate-specific antigen (PSA) between the groups. T-score was the lowest and phosphorus concentration was the highest in the PCa group. Highest PSA, proteins, calcium, and Hekal's formula score were found in the BPH group. Patients with PCa were more frequent GG+GA carriers of 5-HT1B 1997A/G gene polymorphism (p=0.035). Univariate regression analysis showed association of PCa-treated subjects with age (p=0.010) and 5-HT1B genetic polymorphism (p=0.018). Antiandrogen therapy affects T-score (p=0.017), serum phosphorus (p=0.008), glucose (p=0.036), and total proteins (p=0.050). Multivariate-stepwise logistic regression analysis showed the significant association of treated PCa with age (p=0.028) and inorganic phosphorus (p=0.005), and a marginal association with ultrasonographic T-score (p=0.052). CONCLUSIONS: Antiandrogen therapy might induce bone mineral loss in elderly PCa patients. Preliminary data imply that the genetic variants of the 5-HT1B receptor might be associated with PCa.

Effect of electromagnetic radiofrequency radiation on the rats' brain, liver and kidney cells measured by comet assay.

The goal of study was to evaluate DNA damage in rat's renal, liver and brain cells after in vivo exposure to radiofrequency/microwave (Rf/Mw) radiation of cellular phone frequencies range. To determine DNA damage, a single cell gel electrophoresis/comet assay was used. Wistar rats (male, 12 week old, approximate body weight 350 g) (N = 9) were exposed to the carrier frequency of 915 MHz with Global System Mobile signal modulation (GSM), power density of 2.4 W/m2, whole body average specific absorption rate SAR of 0.6 W/kg. The animals were irradiated for one hour/day, seven days/week during two weeks period. The exposure set-up was Gigahertz Transversal Electromagnetic Mode Cell (GTEM--cell). Sham irradiated controls (N = 9) were apart of the study. The body temperature was measured before and after exposure. There were no differences in temperature in between control and treated animals. Comet assay parameters such as the tail length and tail intensity were evaluated. In comparison with tail length in controls (13.5 +/- 0.7 microm), the tail was slightly elongated in brain cells of irradiated animals (14.0 +/- 0.3 microm). The tail length obtained for liver (14.5 +/- 0.3 microm) and kidney (13.9 +/- 0.5 microm) homogenates notably differs in comparison with matched sham controls (13.6 +/- 0.3 microm) and (12.9 +/- 0.9 microm). Differences in tail intensity between control and exposed animals were not significant. The results of this study suggest that, under the experimental conditions applied, repeated 915 MHz irradiation could be a cause of DNA breaks in renal and liver cells, but not affect the cell genome at the higher extent compared to the basal damage.

The genotoxic risk in health care workers occupationally exposed to cytotoxic drugs--a comprehensive evaluation by the SCE assay.

Present study aimed at an integral assessment of sister chromatid exchange (SCE) frequencies in the health care workers occupationally exposed to cytostatics. The results of 500 individual analyses were evaluated. Drug handling practice was investigated in parallel and the results showed that cytostatics are mostly prepared outside hospital pharmacy (98%) and mainly handled by nurses (96%). Mean frequency of SCE was 5.63 +/- 2.28, while HFC represented 9.65% of the cells analysed. Both values were higher compared to previously established control values for Croatian population. The duration of exposure, profession, age, gender, smoking habit, medical exposures, and simultaneous exposure to other occupational mutagens significantly contributed to SCE and HFC values. The usefulness both biomarkers in the assessment of cytogenetic damage is confirmed. Since current practice in Croatian hospitals does not include regular monitoring of workplaces, to ensure maximal occupational safety, a surveillance on exposed health care workers, including periodic biomonitoring, is recommended.

Cholinesterase-inhibiting and genotoxic effects of acute carbofuran intoxication in man: a case report.

Carbofuran belongs to the group of N-methylcarbamate insecticides used for the control of soil-dwelling and foliar-feeding insects in various crops; its consumption totals approximately 20,000 tonnes per year. Although the neurological effects on human beings have been well documented, little is known on its impact on the genome. A 38-year-old, healthy male worker employed in a carbofuran production facility accidentally inhaled the dust of the active ingredient carbofuran. Thirty minutes later, he experienced weakness, fatigue, perspiration, breathing difficulties, cephalalgia, disorientation, abdominal pain and vomiting. Blood samples were taken to measure cholinesterase activity, and to perform the alkaline comet assay and micronucleus assay combined with pancentromeric probes. Analyses were repeated 72 hr after intoxication and compared with the results obtained from regular monitoring conducted 10 days prior to the accident. Cholinesterase activity showed the highest correlation with the number of apoptotic cells, comet assay tail length, and number of long-tailed nuclei, suggesting that these are the genomic end-points primarily affected by carbofuran intake. Only a weak correlation was detected for the total number of micronuclei, centromere-containing micronuclei and nuclear buds. Since those end-points increased significantly 72 hr after the accident, they could be considered as late biomarkers of the effects of carbofuran intoxication. The results of this report suggest that, in the interests of higher standards in risk assessment and health hazard protection, periodical medical examination of carbamate-exposed populations should include genotoxicity testing in addition to the assessment of cholinesterase activity.

Association of toxic and essential metals with atopy markers and ventilatory lung function in women and men.

The association of age, smoking, alcohol, superoxide dismutase (SOD), glutathione peroxidase (GPx), blood lead (BPb) and cadmium (BCd) levels, and serum levels of copper (SCu), zinc (SZn) and selenium (SSe) with atopic status and ventilatory function was examined in the groups of 166 women and 50 men with no occupational exposure to metals or other xenobiotics. Markers of atopy included serum total IgE, skin prick test (SPT) to common inhalatory allergens, non-specific nasal reactivity (NNR) and non-specific bronchial reactivity (NBR). Parameters of ventilatory function included forced vital capacity (FVC) and forced expiratory volume in the first second (FEV(1)). Significantly higher BPb, SZn, IgE and prevalence of positive SPT, and lower SCu and NNR was found in men than in women. Fifteen women taking female sex hormones (HT) had significantly higher SCu than women without HT. Regression models showed significant inverse associations between IgE and SCu (P=0.021) and NNR and SCu (P=0.044) in women. When excluding women with HT, the association of SCu and total IgE became of borderline significance (P=0.051), association between SCu and NNR disappeared, and significant positive association between total IgE and BPb emerged (P=0.046). In men, significant inverse association was found between positive SPT and SSe, and between NBR and SSe. A decrease in FVC% and FEV(1)% was associated with an increase in smoking intensity (P<0.001) and a decrease in SZn (P=0.043 and P=0.053, respectively). These results were observed at the levels of the metals comparable to those in general populations worldwide. The observed differences between men and women may partly be explained by different levels of relevant toxic and essential metals, and their combination. The role of female HT in associations of atopy markers and SCu should be further investigated.

Occupational allergic contact dermatitis from azithromycin in pharmaceutical workers: a case series.

BACKGROUND: Reports on hypersensitivity reactions to azithromycin associated with therapy or occupational exposure have been rare. OBJECTIVES: A case series describing clinical characteristics, diagnostic pathways and risk factors in occupational allergic contact dermatitis (ACD) caused by azithromycin in pharmaceutical workers is presented. PATIENTS/METHODS: 7 out of 21 pharmaceutical workers exposed to powdered intermediate and final substances in azithromycin synthesis were referred with workplace-related skin and respiratory symptoms. They all underwent diagnostic procedure involving medical history and examination, patch testing with standard allergens and azithromycin, prick testing with inhalatory allergens and total immunoglobulin E measurement. RESULTS: Airborne ACD caused by azithromycin was established in 4 examined workers with positive patch test to azithromycin. 2 workers additionally had positive patch test to intermediate substances. Occupation-related symptoms of urticaria, rhinoconjunctivitis, laryngitis and/or dyspnoea were described in additional 2 workers without clearly positive patch test to azithromycin. 2 atopic workers had a shorter asymptomatic period between the beginning of the exposure to azithromycin and occurrence of skin symptoms than non-atopics (2-3 months versus 1-3 years, respectively). CONCLUSIONS: Our results suggest that daily manipulation with powdered azithromycin and intermediates is a main route of sensitization. Besides contact sensitization, other possible workplace-related azithromycin hypersensitivity reactions are indicated.

Sick building syndrome: psychological, somatic, and environmental determinants.

The authors aimed to examine potential relationships between work-related symptoms attributed to sick building syndrome (SBS) and certain psychological, somatic, and environmental factors. The multidisciplinary, cross-sectional study comprised 171 female subjects working in air-conditioned and naturally ventilated nonindustrial office buildings. The authors collected information concerning symptoms related to SBS and made assessments of quality of life by using appropriate questionnaires. They assessed the women's levels of emotional stability or neuroticism using the Cornell Index. They determined skin and airway reactivity markers and indoor microclimate data by using standardized methods. The study showed that the subjects had a high prevalence of fatigue (60.2%), sore and dry eyes (57.9%), and headache (44.4%), as well as a generally high score according to the SBS Index. Neuroticism and subjectively estimated physical health as well as the type of building ventilation significantly contributed to the prediction of the SBS Index, explaining 15% of the variance.

Analysis of dust samples from urban and rural occupational environments in Croatia.

This study estimated the exposure to dust mites in various occupational environments in Croatia. In total, 29 occupational dust samples were collected: 10 from urban areas (offices, archive of an insurance company, tobacco, paper-recycling, fish-processing and textile plants, animal unit for experimental rats, winery), nine from rural areas (barley, hay, animal food and flour warehouses, tailor's shops, wood processing plant, swine confinement house, grocer's storeroom), and 10 samples from cabins of five fishing boats (five floor and five bed samples). Mites were microscopically identified, and the levels of Der p 1, Der f 1, and Der 2 allergens measured using the DUSTSCREEN test (Heska AG, Switzerland). Microscopy showed no mites in urban areas. Pyroglyphid mites (D. pteronyssinus) were found in all bed samples from fishing boats. Non-pyroglyphid mites were found in samples taken from barley, hay and animal food warehouses, the swine confinement house, grocer's storeroom, and fishing boats. Pyroglyphid mite allergens were detected in eight of 10 dust samples from the fishing boats. Median levels of Der p 1, Der f 1, and Der 2 in cabin bed samples were 10 microg g(-1), 0.2 microg g(-1), and 3.5 microg g(-1), respectively. Our findings on fishing boats suggests that pyroglyphid mites could be considered work-related allergens for fishermen. The results of this study confirmed non-pyroglyphid mites as occupational risk factors in various rural environments.

Results of clinical-toxicological assessments performed in the Poison Control Centre in Zagreb over a 10-year period.

The aim of this study was to see which harmful substances and which occupational settings most often required toxicological assessment, to evaluate exposure data provided by employers and to see to what extent could this assessment rely on actual measurements of harmful substances in a working environment. We reviewed the documentation that was submitted for toxicological assessment in all patients referred from occupational health physicians between 1992 and 2001. From 1992 to 2001, the Poison Control Centre performed a total of 260 toxicological evaluations of occupational exposure to harmful chemicals. In 162 cases (62%), measurements of harmful substance concentrations in the working environment would have been of primary significance for the best comparison of potential adverse effects and the level of exposure. The most frequent was exposure to organic solvents in the production line and the use of various paints and varnishes, adhesives and thinners in shoe, chemical and metal-processing industry. Follows exposure to respiratory irritants, mostly in plastic and metal processing. However, measurement data of harmful substances in the working environment were available only in 24 cases, that is, in 9% of all documents submitted for toxicological assessment. Exposure to organic solvents is characteristic for a large number of work places in industry and small enterprises in Croatia, and it is necessary to carry out a more comprehensive study about the real levels of exposure and modes of effective control. It is important because the EU regulations on the indicative occupational exposure limits (OELs) of harmful substances in the working environment, that will soon be implemented into Croatian legislation, recommend a reduction of maximum allowable concentrations (MAC) for commonly used solvents.

[Exposure and allergy to dust mites in general and working environment in Croatia]. / Izlozenost i alergija na prasinske grinje u opcem i radnom okolisu u Hrvatskoj.

This paper gives a review of the most important impacts of exposure to dust mites in general and working environment on human health. The Institute for Medical Research and Occupational Health in Zagreb, Croatia, has been investigating the frequency and exposure levels of allergies to pyroglyphid and non-pyroglyphid mites in Croatia for the last 10 years. Investigations were performed in general urban and rural population from the inland and coastal Croatia, and several industrial inland populations occupationally exposed to organic dusts. Mite species and levels of pyroglyphid mites allergens (Der p 1, Der f 1) were established in house dust samples taken from the floors of bedrooms and living rooms and in several industrial dust samples. The frequency of allergies to pyroglyphid mites in general urban population of inland Croatia is about 20%, with significant general indoor exposure to these mites (median value for Der p 1: 0.85 microg/g of dust). General adult population of the coastal region had a significantly higher exposure to pyroglyphid mites (median value for Der p 1: 4.5 microg/g of dust), yet showed a significantly lower frequency of allergies to these mites (about 5%). New studies are necessary to investigate possible genetic and environmental factors involved in the mechanisms which protect coastal population from the development of mite allergy. Acarological and statistical analyses have shown that the high frequency of sensitisation to non-pyroglyphid mites found in the general and working populations of the inland region is not related to environmental exposure to these mites, but to the cross-reactivity between pyroglyphid and non-pyroglyphid mites and to false positive skin reactions in prick testing, particularly to T. putrescentiae. So far, results do not indicate that pyroglyphid mites are occupational allergens in paper-recycling, fish-processing and tobacco-processing.

Asbestosis in the Republic of Croatia.

Croatians have been exposed to asbestos in the shipbuilding and asbestos-cement industries since 1945. The first cases of asbestosis were reported in 1961; 317 cases were recorded from 1990 to 2000. The Croatian Cancer Registry recorded 248 malignant pleural mesotheliomas between 1991 and 1997, two thirds of which were attributable to occupational exposures to asbestos. The Croatian Asbestosis Patient Association was founded in 1998 to help victims. Croatian law defines the employer's responsibility for work-related health damage and compensation, but average legal proceedings for asbestosis claims take about seven years. Croatian law does not ban the manufacture and import of asbestos. Croatia as a transitional country is subject to socioeconomic pressures. Future approaches to the asbestos issue will depend on revised regulations, which are expected to conform to recommendations of the European Union by 2005.

Erythropoietic changes in rats after 2.45 GJz nonthermal irradiation.

The purpose of this study was to observe the erythropoietic changes in rats subchronically exposed to radiofrequency microwave (RF/MW) irradiation at nonthermal level. Adult male Wistar rats (N=40) were exposed to 2.45 GHz continuous RF/MW fields for 2 hours daily, 7 days a week, at 5-10 mW/cm2. Exposed animals were divided into four subgroups (n=10 animals in each subgroup) in order to be irradiated for 2, 8, 15 and 30 days. Animals were sacrified on the final irradiation day of each treated subgroup. Unexposed rats were used as control (N=24). Six animals were included into the each control subgroup. Bone marrow smears were examined to determine absolute counts of anuclear cells and erythropoietic precursor cells. The absolute erythrocyte count, haemoglobin and haematocrit values were observed in the peripheral blood by an automatic cell counter. The bone marrow cytogenetic analysis was accomplished by micronucleus (MN) tests. In the exposed animals erythrocyte count, haemoglobin and haematocrit were increased in peripheral blood on irradiation days 8 and 15. Concurrently, anuclear cells and erythropoietic precursor cells were significantly decreased (p < 0.05) in the bone marrow on day 15, but micronucleated cells' frequency was increased. In the applied experimental condition, RF/MW radiation might cause disturbance in red cell maturation and proliferation, and induce micronucleus formation in erythropoietic cells.

Exposure levels and skin reactivity to German cockroach (Blattella germanica) in Croatia.

AIM: To evaluate German cockroach (Blattella germanica) allergen levels in house dust and skin reactivity to German cockroach in adult atopic and non-atopic subjects in inland areas of Croatia. METHODS: Blattella germanica group 2 (Bla g 2) allergen was measured using the enzyme-linked immunosorbent assay (ELISA) on test strips (Dustscreen(TM) test, Heska AG, Switzerland) in 94 house dust samples collected from living room and bedroom floors, 35 from rural and 59 from urban areas. Skin prick testing with common inhalatory allergens, Blatella germanica, storage mites Lepidoglyphus destructor and Tyrophagus putrescentiae (ALK-Abello, Denmark) was performed in 187 adult outpatients, 131 from urban and 56 from rural areas. Total serum IgE levels were measured using the ELISA method. Subjects with relevant respiratory and/or skin symptoms, at least one positive skin prick test, and/or increased total IgE were considered atopic. RESULTS: Positive skin prick test to cockroach was observed in 18/187 subjects (9.6%). The frequency of skin prick test positive subjects to cockroach was higher in atopic than in non-atopic subjects, but not significantly (12.2% vs. 4.7%; p=0.098). Of 15 atopic subjects with positive skin prick test to cockroach, 14 also had positive skin prick test to storage mites, 8 to house dust mites, 1 to pollens, and none to cockroach only. Positive skin prick test to storage mites was the only factor which significantly increased the risk for having positive skin prick test to cockroach (n=187; odds ratio, 109.82; 95% confidence interval, 2.06- 5853.5; p= 0.020). In all 94 house dust samples, Bla g 2 was not detectable. CONCLUSIONS: Our results suggest that there is no relevant exposure to cockroach allergen in house dust samples from inland areas of Croatia. Consequently, positive skin prick test to cockroach is rare in adult subjects, even in atopics. Positive skin prick test to cockroach in atopics is in the majority of cases related to positive skin prick test to storage mites, probably due to cross-reactivity.

[Allergic disorders of the respiratory system and skin as a public health problem]. / Alergijski poremecaji disnog sustava i koze kao javnozdravstveni problem.

The prevalence of allergic diseases is rapidly increasing over the last 40 years, especially in most industrialized countries of the world. Manifestations of allergic diseases are observed in about 35% of the general population. In this paper, the most frequent allergic respiratory and skin diseases are described (rhinitis, asthma, atopic eczema/dermatitis syndrome, contact eczema/dermatitis, urticaria). The most important individual and environmental factors involved in the occurrence of allergic diseases are described: genetic predisposition, exposure to allergens, environmental pollution and modern life style are discussed. The results of our investigations related to the prevalence of allergy markers in general and working population are presented. The preventive measures concerning allergic diseases are considered.

Pre-employment evaluation of atopy and contact sensitisation in the prevention of allergy-related diseases.

The aim of this study was to determine the prevalence of markers of atopy and contact sensisation in asymptomatic young adults and to assess their role in pre-employment screening. The study included 351 subjects, of whom166 women (mean age 28.0 + / - 6/4 years) and 185 men (mean age 26.3 + / - 5.4 years). The pre-employment examination commissioned by a pharmaceutical company included a questionnaire, the patch test with the European standard series of contact allergens prick test with common inhalatory allergens, and the serum-specific IgE measurement. According to the medical history 115/166 (69.3%) women and 142/185 (76.8%) men were asymptomatic, but 28 (24.3%) asymptomatic women and 40 (28.2%) showed atopy and/or contact sensitization. Pre-employment allergy examination can be considered a reliable detection procedure for the majority of asymptomatic persons with atopy and contact sensitization. The knowledge of these conditions gives the opportunity for secondary prevention and better diagnostic validation of occupational allergic diseases.

Commercial rodent feed as an occasional cause of morbidity and mortality in a rat breeding colony.

In the last fifteen years there were several feed-related outbreaks of morbidity and mortality in the Institute's breeding colony of Wistar rats. The last event took place in April 1999, one month after the use of a new supply of the usual standard rodent feed. Animals did not thrive and manifested generalised oedema, hypoalbuminaemia, elevated liver enzymes, and high mortality. The effect of feed was assessed first by feeding a group of sick females during 14 days with either suspected feed (A-March) or with the earlier supply of feed (A-January) of the same producer. Then a group of healthy male rats Y59 from another breeding colony was fed either suspected feed (A-March) or feed from another producer (feed B). Although neither chemical nor microbiological deviation in feed analysis had been detected, decreased consumption and slower body weight gain in all animals fed with feed A-March suggested an association between this batch of feed and the increased morbidity in those animals. Eventually, the entire rat colony was put down and replaced with a new breed which was given a new brand of feed.

Adamantyl tenocyclidines--adjuvant therapy in poisoning with organophosphorus compounds and carbamates.

The objective of this study was to evaluate the efficacy of thienyl phencyclidine (tenocyclidine, TCP) and its newly synthesized adamantyl derivatives containing piperidine (TAPIP), pyrolidine (TAPIR) and morpholine (TAMORF) groups, which were tested with or without standard therapy in mice poisoned with organophosphates (OPs) and carbamates. These compounds with potential activity at the N-methyl- D-aspartate and muscarinic receptors showed low acute toxicity, having LD50 values varying from 106.00 mg/kg (TCP) to >504.00 mg/kg body weight (TAMORF). TCP and its adamantyl derivatives were administered intraperitoneally (2.5 mg/kg body weight) together with atropine (10.0 mg/kg body weight) and with or without 1/4 LD50 of the oxime HI-6. Each compound administered with atropine had a therapeutic effect against poisoning with carbamates propoxur, aldicarb and Ro 02-0683 (protective ratio of tenocyclidines was from 3.99 LD50 of aldicarb to >16.00 LD50 for propoxur). However, the efficacy of those compounds in combination with atropine was lower against poisoning with the OP insecticide dichlorvos (DDVP) and chemical warfare agents soman and tabun. In soman-poisoned mice, the best therapeutic effects were obtained with the combination of HI-6 plus atropine and test compounds, with protective ratios being from 5.40 to 7.12 LD50 of soman. The results suggest that TCP and adamantyl tenocyclidines could be used in combination with atropine as antidotes in carbamate poisoning and as adjuvant therapy to HI-6 and atropine in soman poisoning.