Iron retention in iron-fortified rice and use of iron-fortified rice to treat women with iron deficiency: A pilot study.

OBJECTIVES: 1. Evaluate the effect of washing and cooking iron-fortified rice on iron retention and bioavailability. 2. Evaluate the effect of iron-fortified rice on women with iron deficiency anemia. METHODS: 1. Iron-fortified rice (18 mg/100 g as FeSO4) was cooked in Baton Rouge, Louisiana (C), rinsed and cooked (RC), fried and cooked (FC), cooked with extra water (CW), or soaked and cooked with extra water (SCW), and iron retention was determined. 2. Rice samples were cooked in Kampala, Uganda in a lab (C-Uganda) and households using traditional cooking method (TC-Uganda) and iron retention were determined. 3. Seventeen women with iron deficiency (low iron and/or low ferritin) anemia were randomized to 100 g/d of rice (two cooked 0.75 cup servings) for two weeks containing 18 mg/d iron (supplemented) or 0.5 mg/d iron (un-supplemented). Hemoglobin and hematocrit were evaluated at baseline and 2 weeks with other measures of iron metabolism. RESULTS: 1. Iron retention, from highest to lowest, was (C), (RC), (FC), (C-Uganda), (CW), (SCW) and (TC-Uganda). 2. Seventeen women were randomized and 15 completed the study (hemoglobin 10.6 ± 1.6 g, hematocrit 33.7 ± 4.1%), 9 in the iron-fortified rice group and 6 in the un-fortified rice group. The iron-fortified group had a greater increase in hemoglobin (0.82 g, p = 0.0035) and Hematocrit (1.83%, p = 0.0248) with directional differences in other measures of iron metabolism favoring the iron-fortified group. CONCLUSIONS: Iron-fortified rice increased hemoglobin and hematocrit in women with iron-deficient anemia. Iron deficiency and anemia are widespread in Southeast Asia and Africa and undermine development in these regions.

Dysmenorrhea and Stress among the Nepalese Medical Students.

Background Dysmenorrhea is the most common gynecological disorder in women of reproductive age with implications as reduced quality of life and school absenteeism. Mental stress is possibly the most important known predisposing factor for primary dysmenorrhea. Objective This study aims to assess the relationship between stress and dysmenorrhea amongst the Nepalese medical students. Method This is cross-sectional descriptive study, conducted from 1st Dec. 2012 to 31st Jan. 2013. The study was conducted in Kathmandu University School of Medical Sciences. A total of 184 participants consented for this study and each one was given a questionnaire to complete. This study included only unmarried nulliparous, healthy (all through first to final years) female medical students, in age group of 16 to 24 years. Result The mean age of the participants was 19.43(±3.9) years. Among them, 67% of the participants experienced dysmenorrhea. Of them, 85% experienced increase in frequency and severity of dysmenorrhea after joining medical college. Similarly, 65% of participants considered medical education to be stressful. Of participants experiencing dysmenorrhea, 29.45% missed classes and 17.39% participants had positive family history of dysmenorrhea in first and second degree relatives. Conclusion The present study indicated a positive relationship between psychological stress and dysmenorrhea. Dysmenorrhea is the leading cause of recurrent short-term school absence in young ladies; this issue certainly needs to be addressed.

Microbial transport into groundwater from irrigation: Comparison of two irrigation practices in New Zealand.

UNLABELLED: Rising demand on food is leading to an increase in irrigation worldwide to improve productivity. Irrigation, for pastoral agriculture (beef, dairy and sheep), is the largest consumptive use of water in New Zealand. There is a potential risk of leaching of microbial contaminants from faecal matter through the vadose zone into groundwater. Management of irrigation is vital for protection of groundwater from these microbial contaminants and maintain efficient irrigation practices. Our research investigated flood and spray irrigation, two practices common in New Zealand. The aim was to identify the risk of microbial transport and mitigation practices to reduce or eliminate the risk of microbial transport into groundwater. Cowpats were placed on lysimeters over a typical New Zealand soil (Lismore silt loam) and vadose zone and the leachate collected after irrigation events. Samples of both cowpats and leachate were analysed for the microbial indicator Escherichia coli and pathogen Campylobacter species. A key driver to the microbial transport derived from the model applied was the volume of leachate collected: doubling the leachate volume more than doubled the total recovery of E. coli. The persistence of E. coli in the cowpats during the experiment is an important factor as well as the initial environmental conditions, which were more favourable for survival and growth of E. coli during the spray irrigation compared with the flood irrigation. The results also suggest a reservoir of E. coli surviving in the soil. Although the same was potentially true for Campylobacter, little difference in the transport rates between irrigation practices could be seen due to the poor survival of Campylobacter during the experiment. Effective irrigation practices include monitoring the irrigation rates to minimise leachate production, delaying irrigation until 14days post-cowpat deposition and only irrigating when risk of transport to the groundwater is minimal. AIM: To compare the risk of microbial contamination of groundwater from cowpats using two irrigation practices onto pasture.

Cost-benefit analysis of avian influenza control in Nepal.

Numerous outbreaks of highly pathogenic avian influenza A strain H5N1 have occurred in Nepal since 2009 despite implementation of a national programme to control the disease through surveillance and culling of infected poultry flocks. The objective of the study was to use cost-benefit analysis to compare the current control programme (CCP) with the possible alternatives of: i) no intervention (i.e., absence of control measures [ACM]) and ii) vaccinating 60% of the national poultry flock twice a year. In terms of the benefit-cost ratio, findings indicate a return of US $1.94 for every dollar spent in the CCP compared with ACM. The net present value of the CCP versus ACM, i.e., the amount of money saved by implementing the CCP rather than ACM, is US $861,507 (the benefits of CCP [prevented losses which would have occurred under ACM] minus the cost of CCP). The vaccination programme yields a return of US $2.32 for every dollar spent when compared with the CCR The net present value of vaccination versus the CCP is approximately US $12 million. Sensitivity analysis indicated thatthe findings were robust to different rates of discounting, whereas results were sensitive to the assumed market loss and the number of birds affected in the outbreaks under the ACM and vaccination options. Overall, the findings of the study indicate that the CCP is economically superior to ACM, but that vaccination could give greater economic returns and may be a better control strategy. Future research should be directed towards evaluating the financial feasibility and social acceptability of the CCP and of vaccination, with an emphasis on evaluating market reaction to the presence of H5N1 infection in the country.

Prevalence of Gall Stones in Liver Cirrhosis.

INTRODUCTION: Increased incidence and prevalence of gallstones in liver cirrhosis has already been reported by many studies. This study aimed to investigate the prevalence of gallstone disease in Nepali patients with LC and to identify risk factors for gallstone formation. METHOD: Consecutive patients of LC presenting to liver clinic from January, 2010 to December, 2012 were evaluated for GS by ultrasonography at their first visit. Liver cirrhosis was diagnosed on the basis of clinical features, laboratory parameters, ultrasonography, and/or histopathology. RESULT: Two hundred and twenty four LC patients were studied. Male to female ratio was 2.3:1. Alcohol was the major etiological factor for LC followed by hepatitis B, alone or in conjunction with alcohol. Seventy-four patients (33%) were found to have GS. Incidence of GS was more in advance stage of cirrhosis. There was no significant correlation between formation of GS and etiology of LC, except for the HCV related liver cirrhosis, in which it was present in 39% of the patients. More the advance disease,more was the incidence as 57% of Child-C patients had GS. Portal vein diameter was also associated with GS formation. When portal vein diameter was more than 13 mm, there was more GS formation. CONCLUSIONS: One third of the patients of LC showed GS at the presentation. Patients with HCV related cirrhosis are more prone to develop GS than other. Severity of the disease and portal vein diameter was found to be associated with GS formation.

A survey of enteric bacteria and protozoans in fresh bovine faeces on New Zealand dairy farms.

AIMS: To determine the counts and/or prevalence in fresh bovine faeces of Escherichia coli, enterococci, Campylobacter, Salmonella, shiga toxin-producing E. coli (STEC), Giardia and Cryptosporidium, as inputs to numerical models designed to estimate microbial loadings on pasture grazed by cattle in New Zealand. METHODS AND RESULTS: In each season over one year, samples of freshly deposited bovine faeces were collected from four New Zealand dairy farms (n = 155), and enumerated for E. coli, enterococci, Campylobacter, Giardia and Cryptosporidium. They were also tested for the presence of Salmonella and STEC. The overall median bacterial counts (g(-1) wet weight) were E. coli- 5.9 x 10(6); enterococci - 1.3 x 10(4); Campylobacter- 3.9 x 10(5). All counts were highly variable within and between samplings, and few seasonal or regional patterns emerged. However, mean Campylobacter counts were consistently higher in spring. No Salmonella spp. was detected, and only two samples were positive for STEC. Cryptosporidium and Giardia were isolated from 5.2% and 4.5% of the samples, respectively, yielding low numbers of (oo)cysts (1-25 g(-1) and 1-17 g(-1), respectively). CONCLUSIONS: Fresh bovine faeces are a significant source of E. coli, enterococci and Campylobacter on New Zealand pastures, although numbers are likely to vary markedly between faecal samples. SIGNIFICANCE AND IMPACT OF THE STUDY: The study provides the first significant set of indicator and pathogen counts for one of the largest sources of faecal contamination of natural waters in New Zealand, and will be used to model these inputs.

Pattern of poisoning cases in Emergency Department of Kathmandu Medical College Teaching Hospital.

OBJECTIVE: This study was conducted to determine the pattern and severity of poisoning cases in Emergency Department of Kathmandu Medical College Teaching Hospital, Kathmandu, Nepal (KMCTH). DESIGN: Retrospective observational study. MATERIALS AND METHODS: Hospital records of all admissions to the Emergency Department of Kathmandu Medical College Teaching Hospital (KMCTH) following acute poisoning were revised and all data from February 2007 to February 2008 were analyzed retrospectively. RESULTS: This retrospective observational study was performed on 148 cases of poisoning who attended Emergency Department of KMCTH over a period of one year. The overall male to female ratio was 1.05:1. Poisoning was most common in the age group 21-30 years (40.5%). The most common causes of poisoning in adults were organophosphorous compounds and in children was kerosene oil. Oral route (79.05%) was the most common route of administration. 66.2% of cases were intentional poisoning for suicidal attempt. Students (43.9%) and service holders (18.9%) were commonly involved in poisoning. CONCLUSION: It was seen that adult between 21-30 years of age were more prone to suicidal poisoning with organophosphorous compounds and children of 1-10 years of age were more susceptible to accidental poisoning with kerosene oil.

Polymorphism of debrisoquine hydroxylation among Finns and Lapps.

Debrisoquine hydroxylation polymorphism was studied in 155 Finns and 70 Lapps. The frequency of the poor metabolizer phenotype was 3.2% among Finns (95% confidence interval 0.4-6.0%) and 8.6% among Lapps (95% confidence interval 2.0-15.1%).

Cardiovascular and sedative alpha-adrenoceptor effects of detomidine-like arylalkyl imidazoles and associated derivatives.

The effects of detomidine (4-[(2,3-dimethylphenyl)methyl]-1H-imidazole, Domosedan) and its congeners, MPV compounds, are evaluated in the cardiovascular system and related to their sedative action using clonidine and xylazine for reference purposes. The structure of the MPV compounds had been modified with methyl substituents in the phenyl ring, with differing lengths in the alkyl bridge, and with variations in the imidazole terminus. The lipophilicity of the test compounds had been estimated in terms of apparent partition coefficients in the octanol/buffer (pH 7.4, 24-26 degrees C) using the HPLC technique. The lipophilicity of the MPV compounds was found to be higher than for either clonidine or xylazine, suggesting a more rapid penetration into the central nervous system. Some of these 21 MPV compounds were hypotensive and bradycardic in anaesthetized rats. Interestingly a number of these MPV compounds were only bradycardic but not clearly hypotensive after i.v. administration to anaesthetized rats, this being most obvious in the case of the 2,5-dimethylphenyl derivative MPV 867. A further characteristic distinguishing between the central and peripheral alpha-adrenoceptors regulating cardiovascular tone was a distinct inability of some derivatives active at peripheral cardiac presynaptic (pithed rats) and central (young chicks) alpha 2-adrenoceptors to reduce blood pressure in anaesthetized rats. The sedative action of the compounds after i.m. injection into 2- to 5-day-old chicks was in general related to their central hypotensive and bradycardic effect in anaesthetized rats, and with peripheral vasopressor and sympatho-inhibitory activity in pithed rats.(ABSTRACT TRUNCATED AT 250 WORDS)

The metabolism of 2,5-diphenyloxazole (PPO) in human lymphocytes and rat liver microsomes.

The oxidative metabolism of 2,5-diphenyloxazole (PPO) is associated with 3-methylcholanthrene inducible cytochrome P-450. The major metabolite formed has m/z of 237, corresponding to hydroxylated PPO. All the possible hydroxylated metabolites of PPO were synthesized and characterized, enabling the assignment of a structure for the major metabolite and two minor metabolites. The metabolites are easily extracted and their fluorescence is quantifiable in alkaline medium with a sample fluorescence to blank fluorescence ratio of 400:1. A sensitive HPLC assay of PPO metabolism was also developed. PPO metabolism is readily catalyzed by 3-methylcholanthrene-induced rat liver microsomes and strongly inhibited by alpha-naphthoflavone, but poorly inhibited by metyrapone or SKF 525A, indicating the involvement of cytochrome P-448 or P1-450 in the metabolism of PPO. With human lymphocytes the method has proven to be a good indicator of "aryl hydrocarbon hydroxylase" (AHH) activity, correlating well with AHH assays using benzo(alpha)pyrene (BP) as a substrate. Both the induced BP and PPO metabolism by human lymphocytes is inhibited by alpha-naphthoflavone, but not by metyrapone.

Aryl hydrocarbon hydroxylase in lymphocytes and lung tissue from lung cancer patients and controls.

The inducibility of aryl hydrocarbon hydroxylase (AHH) activity in peripheral mitogen-treated lymphocytes, and of AHH and other monoxygenase activities in lung samples, was studied in 41 patients--34 with pulmonary carcinoma, 4 with a benign lung tumour and 3 with chronic obstructive pulmonary disease. Lymphocyte AHH induction alone was studied in 43 non-smoking and 37 smoking surgical patients. Absolute induced and non-induced AHH activities were at about the same level in the lymphocytes from the lung cancer patients as in those from the non-smoking controls, whereas the activities in smoking controls were about 100% higher. The mean inducibility ratios were very similar in all groups, ranging from 4.4 in the benign tumour patients to 5.4 in both control groups. Thymidine incorporation was on average about 40% lower in the lymphocytes from the lung cancer patients. AHH activity was detectable in all the peripheral lung samples, both normal or tumorous tissue, and its inter-individual variation was more than 67-fold. ECDE activity was also detectable in all the samples studied and its correlation with AHH activity was statistically significant (r = 0.888), suggesting that the same enzyme metabolizes both substrates. ERDE was detectable only in the samples with the highest AHH and ECDE activities. There was no correlation between basal or induced lymphocyte AHH activities and lung tissue AHH activity, but there were statistically significant correlations between lung AHH activity and the inducibility ratio with (r = 0.618) or without correction by thymidine incorporation (r = 0.442). These correlations suggest that there are common regulatory factors for AHH inducibility in different tissues. No significant difference in any drug metabolism parameter measured was observed between the lung cancer patients and the controls.

Hepatic drug metabolism and the activities of NADPH generating enzymes and glucose-6-phosphatase in phenobarbital treated genetically obese (ob/ob) mice.

We aim to evaluate the effects of phenobarbital (PB) on the liver drug metabolism, NADPH production capacity and terminal gluconeogenic enzyme, glucose-6-phosphatase (G6Pase) activity in the diabetic state associated with genetic obesity in mice. The results showed that PB treatment increased the amount of liver total cytochrome P450 (cytP450), a drug metabolizing monooxygenase enzyme in genetically obese, hyperglycemic (ob/ob) mice 6-fold and the total activities of other monooxygenase enzymes NADPH cytP450 reductase and 7-ethoxyresorufin O-deethylase (ERDE) 2- and 6.5-fold, respectively. In addition, the regimen increased the liver total activities of two NADPH generating enzymes, 6-phosphogluconate dehydrogenase (6PGDH) and malic enzyme (ME) in obese mice suggesting that the regimen enhanced liver NADPH production capacity in the animals. The data further showed that PB treatment decreased the high hepatic G6Pase activity in obese mice. Both enhanced NADPH generating enzyme activities and lowered G6Pase activity may suppress hepatic glucose output. Since NADPH is required for drug oxidation reactions as a reducing cofactor, high NADPH generating capacity may facilitate liver drug metabolism in vivo. Although the diabetic state in obese mice differs somewhat from that seen in non-insulin dependent diabetic subjects (NIDDs), these findings provide some knowledge about the possible biochemical mechanisms whereby PB treatment normalizes drug metabolism and glycemic control in NIDDs, as has been noted in previous studies.

Evidence for medetomidine as a selective and potent agonist at alpha 2-adrenoreceptors.

The activity on alpha-adrenoreceptors of medetomidine ((+/-)-4-(alpha,2,3-trimethylbenzyl)imidazole), an alpha-methyl derivative of detomidine, has been characterized in vivo and in vitro using detomidine, MPV 207, MPV 295, azepexole, clonidine and xylazine for reference purposes. Medetomidine (1-100 micrograms/kg i.v.) was a hypotensive and bradycardic compound in anaesthetized rats. Furthermore, it induced vasopressor (PD50 1.7 microgram/kg) and sympatho-inhibitory (ID50 1.6 microgram/kg) actions in pithed rats, the effects being antagonized by idazoxan (0.3 mg/kg i.v.) but not by prazosin (0.1 mg/kg i.v.). Medetomidine (30-300 micrograms/kg i.m.) had an alpha 2-adrenoreceptor mediated sedative effect on chicks. Medetomidine was, overall, more potent than detomidine, MPV 207, clonidine, xylazine, MPV 295 or azepexole in central (sedation in the chick) and peripheral (cardiac presynaptic in the pithed rat) actions on alpha 2-adrenoreceptors. Clonidine had, however, about an equal potency to medetomidine in the vascular smooth muscle of the pithed rat. Like detomidine and MPV 295, medetomidine had no agonistic activity in the rat aortic ring, but high concentrations antagonized methoxamine-induced contractions, giving a pA2 value of 5.68 for alpha 1-adrenoreceptor antagonism. The overall lipophilicity (log P') of medetomidine in the octanol/buffer (pH 7.4, 24-26 degrees C, HPLC technique) was 2.80. In summary, the experimental data suggest that medetomidine is a lipophilic compound with selective alpha 2-adrenoreceptor-stimulating properties and high potency. It may, therefore, prove to be a suitable pharmacologic tool for interventions in alpha 2-adrenoreceptor mediated effects in the autonomic nervous system.

Increased sister-chromatid exchange rate and its regression during prolonged incubation in lymphocyte cultures from patients with multiple sclerosis.

Peripheral venous blood lymphocytes from multiple sclerosis patients, cultured for 72 h in the presence of phytohemagglutinin, appeared to have a higher sister-chromatid exchange (SCE) rate than cells from matched controls. Prolongation of the incubation time to 9 days by adding interleukin-2 to the cultures, caused the cells from the MS patients to lose their increased SCE frequency, so that the mean rate no longer differed from that of the controls. The SCE rate of the controls did not change significantly on prolonged incubation.

Re-evaluation of drug-interaction with alpha-adrenoceptors in vivo and in vitro using imidazole derivatives.

The critical spatial dimension requirements for drug interaction with alpha-adrenoceptors were examined using imidazole derivatives MPV 295 and its semi-rigid analogue MPV 305 T (= trans) or MPV 305 C (= cis). The ethenyl bridge bond between the phenyl and imidazole moieties of MPV 305 prevents it achieving the critical spatial dimensions of the phenethylamines (e.g. norepinephrine). MPV 295 (0.03-10 mg/kg i.v.) and the trans-extended MPV 305 T (0.01-1 mg/kg i.v.) were hypotensive and bradycardic in anesthetised rats. In pithed rats, MPV 295 and MPV 305 T induced vasoconstriction, the doses giving a 50 mmHg rise in mean arterial pressure being 34.5 and 11.5 ug/kg, respectively. The pressor activity of MPV 295 was antagonized by idazoxan (1 mg/kg i.v.) but not by prazosin (0.1 mg/kg i.v.), whereas that of MPV 305 T was antagonized by prazosin and to a greater extent by idazoxan. Both compounds inhibited the increase in heart rate produced by electrical stimulation of the cardioaccelerator sympathetic nerve fibres in the pithed rats. The doses which induced a 50% inhibition of sympathetic transmission were 49.0 and 38.0 ug/kg for MPV 295 and MPV 305 T, respectively. This peripheral sympatho-inhibitory action was antagonized by idazoxan. Both compounds inhibited the twitch response of electrically stimulated mouse vas deferens, the pD2 values being 7.59 and 7.89 for MPV 295 and MPV 305 T, respectively. In the rat anococcygeus muscle only MPV 305 T was active (pD2 4.84). The cis-folded MPV 305 C was practically inactive in pithed rats and in rat anococcygeus muscle. According to the results, the strengthening of the ethano bridge of MPV 295 to that of MPV 305 T, thus preventing it fitting into the proposed dimensions of alpha-agonists, does not lead to a decrease in alpha-adrenoceptor mediated activities. Therefore, the spatial dimension requirements among imidazoles are different from those among the phenethylamines, supporting the concept that imidazoles interact differently with alpha-adrenoceptors when compared to the phenethylamines.

Cardiovascular action of detomidine, a sedative and analgesic imidazole derivative with alpha-agonistic properties.

The cardiovascular effects of detomidine, a new veterinary sedative and analgesic imidazole derivative were studied in rats and cats using as reference compound xylazine, a widely employed veterinary antinociceptive and sedative drug with alpha-agonistic potency. Detomidine (1-30 micrograms/kg i.v.) and xylazine (10-1000 micrograms/kg i.v.) had both dose-dependent hypotensive and bradycardiac effects in anaesthetized rats. After i.v. administration of 3-100 micrograms/kg detomidine and 0.1-3 mg/kg xylazine to conscious rats, detomidine was more active in reducing the heart rate than in lowering the blood pressure. In anaesthetized cats, detomidine (1-30 micrograms/kg i.v.) was hypotensive and bradycardiac in a dose-dependent manner. A low dose of detomidine into the vertebral artery was more effective than i.v. application in reducing blood pressure. Idazoxan (0.3 mg/kg i.v. and 0.03 mg/kg into the vertebral artery) antagonized the hypotensive and bradycardiac effects of detomidine injected into the femoral vein or vertebral artery, respectively. In pithed rats, detomidine and xylazine stimulated presynaptic and postsynaptic alpha 2-adrenoceptors, and to a lesser extent postsynaptic alpha 1-adrenoceptors. The results indicate that detomidine is an agonist of central and peripheral alpha 2-adrenoceptors which exerts its hypotensive and bradycardiac effects via activation of the central alpha 2-adrenoceptors.

Medroxyprogesterone acetate and phenobarbital induce NADPH producing enzyme activities in rats with a chemical liver injury.

The administration of medroxyprogesterone acetate (MPA) and phenobarbital (PB) improves liver function in rats with liver damage. This was seen here as increased aryl hydrocarbon hydroxylase (AHH) activity after therapy with MPA or PB in rats with a chemical liver injury, produced by dimethylnitrosamine (DMN). Hepatic glucose-6-phosphatase (G6Pase) activity, an index of glucose metabolism was also normalized in the MPA treated rats. The present study further shows that MPA induced hepatic malic enzyme (ME) and isocitrate dehydrogenase (ICDH) activities and PB enhanced glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH) and ME activities in the DMN pretreated rats. This suggests that MPA and PB enhanced the capacity of altered liver tissue to generate NADPH, a cofactor in the monooxygenase system, which may, in part, enhance the restoration of drug hydroxylation in the rats. Since G6PDH, 6PGDH and ME participate in glucose metabolism, the finding that the compounds influenced these enzymes in distinct ways, may explain the different effects of MPA and PB on the restoration of glucose metabolism.

Peripheral cardiovascular alpha- and beta-adrenergic effects of some hypotensive and bradycardic arylalkyl imidazole derivatives in the rat.

In pithed rats, a series of four alkyl bridge analogues of 4(5)-substituted arylalkyl imidazole induced alpha-adrenoceptor-mediated vasoconstriction and inhibition of electrically stimulated tachycardia. These effects were induced in the order of potency clonidine = MPV 207 greater than MPV 295 greater than MPV 304 greater than MPV 390, correlating with the length of the alkyl bridge between the phenyl and imidazole moieties. The peripheral postsynaptic actions of MPV 207 and MPV 304 were attenuated by prazosin (0.1 mg kg-1 i.v.) and yohimbine (1 mg kg-1 i.v.). The pressor responses induced by MPV 295 were antagonized only by yohimbine (0.3 and 1 mg kg-1 i.v.). The peripheral sympathoinhibitory action of these compounds was antagonized by yohimbine (1 mg kg-1 i.v.). In spontaneously beating rat atria, the MPV compounds showed neither agonistic nor antagonistic activity at cardiac postsynaptic alpha- and beta-adrenoceptors. The results indicate that the hypotensive and bradycardic MPV compounds are agonists at peripheral cardiovascular alpha-adrenoceptors. The extension of the alkyl bridge between the phenyl and imidazole moieties reduces their activity at alpha-adrenoceptors. Finally, MPV 295 seems to be a selective agonist of peripheral alpha 2-adrenoceptors in the cardiovascular system of the pithed rat.

Metabolism of medroxyprogesterone acetate and hepatic drug metabolism activity.

The effect of microsomal enzyme activity on the hepatic metabolism of medroxyprogesterone acetate (MPA), measured in vitro, and the MPA concentrations in liver and plasma were investigated in rats with intact and injured livers before and after MPA therapy. The amount of total MPA metabolites and the activity of drug-metabolizing enzyme system changed in a parallel manner in the livers. The ratio of liver/plasma concentration of MPA was decreased in the liver injury. The hepatic metabolism of MPA is accelerated during MPA treatment in rat.

Genetic and environmental regulation of aryl hydrocarbon hydroxylase in man: studies with liver, lung, placenta, and lymphocytes.

Properties and response smoking of aryl hydrocarbon hydroxylase (AHH) activity in various human tissues are reviewed. In the placenta, induction of AHH by smoking can be demonstrated unequivocally. AHH activity in lung samples is variable, but the relation to current or past smoking is unclear. The effect of cigarette smoking can be readily shown in the rate of antipyrine elimination, although there is no change in AHH activity in liver biopsy samples. The reason for this discrepancy is not known. In peripheral lymphocytes a sort of "memory-effect" of cigarette smoking is retained even after culturing, the nature of this phenomenon remaining unclear. Furthermore, there seem to be many factors affecting AHH induction in peripheral lymphocytes in culture. These data suggest that regulation of AHH activity and induction is tissue-specific, i.e. no systemic regulation is discernible. It is also possible that the P-450 isozyme composition in some tissues masks the induction. Reasons for discrepancies between animal and human data are not clear; however, genuine biological differences and technical difficulties in human studies can be postulated.