Distribution of major and minor alkaloids in tobacco, mainstream and sidestream smoke of popular Indian smoking products

Various Indian smoking products--cigarette, bidi, chutta and a brand of US cigarette--were analysed by gas chromatography-flame ionization detection (GC-FID) for the levels of nicotine and minor tobacco alkaloids in tobacco, mainstream smoke (MS) and sidestream smoke (SS) employing modified smoking standards, namely two puffs/min. The analysis clearly demonstrated relatively higher levels of nicotine and minor tobacco alkaloids in tobacco from bidi (37.7 mg/g) and chutta (34.5 mg/g) when compared with Indian and US cigarettes (14-16 mg/g) studied. Relatively lower levels (SS/MS) of nicotine in SS from bidi and chutta compared with Indian/US cigarettes, suggest that the contribution of nicotine in SS from a single bidi/chutta to environmental tobacco smoke (ETS) is very much less than that of a single Indian/US cigarette. Reduced levels of nicotine in SS of bidi/chutta result in relatively higher deliveries of nicotine in MS as reflected by higher MS/SS values. The observed differences are likely to be due to difference in tobacco processing, burning rate/temperature and design of the smoking product.     

Pharmacokinetics of cyclophosphamide and its metabolites in bone marrow transplantation patients

Classical swine fever virus infection of pigs causes a severe leukopenia and immunosuppression. In the present study, the kinetics of virus infection, and identification of target cells for the virus in peripheral blood were analysed. Virus infection was often not detectable before 5-7 days p.i. A minority of animals yielded detectable infected cells at 3 days p.i., but < 5% PBMC. It was not until 10 days p.i. that this figure increased-to 35-70% PBMC depending on the animal. Detailed analysis of Ficoll-Hypaque-purified PBMC identified the major population to be SWC3+SWC8+CD14+MHCII- granulocytic cells. Microscopic observations determined that these low density granulocytic cells in the PBMC from CSFV infected animals were indeed immature cells. Both the low density granulocytic cells and monocytes were major targets for CSFV infection in the peripheral blood. This is the first demonstration that low density granulocytic cells dominate the blood leukocyte population during CSF, and that such cells are targets for virus infection. The present work also demonstrates that the leukocyte population changes, such as B lymphocyte depletion and the relative dominance of myeloid cells in the blood during CSF, occur before virus infection of the affected cells. Thus, the pathological mechanism therein is not a direct consequence of virus infection.     

Hypothalamic dopamine D1 receptors are involved in the stimulation of prolactin secretion by high environmental temperature in the female sheep

Recent evidence suggests that dopamine, acting via its D1 receptors, may function as a neurotransmitter in intrahypothalamic pathways involved in the stimulation of prolactin secretion. Functional dopamine D1 receptors are present in the ventromedial hypothalamic nucleus (VMH) and we hypothesized that they might be part of a prolactin-stimulatory pathway activated by stress. We tested this hypothesis in a series of experiments on sheep involving two different forms of stressors, audiovisual (barking dog) and high environmental temperature. We attempted to block the stimulation of prolactin secretion by infusion into the VMH of an antagonist specific for the D1 receptor. Ovariectomised, oestradiol-implanted merino ewes were surgically implanted with bilateral guide tubes directed at the VMH. After a 180 min pretreatment period, the ewes either were or were not exposed to a stressor (30 min of barking dog or 120 min at 35 degrees C, 65% relative humidity). D1 receptor antagonist, SCH23390 or vehicle (0.9% saline) was infused into the VMH (1.7 microliters/h, 120 nmol/h) for 60 min prior to and during the stressor period. Blood was sampled every 15 min via jugular cannulae and the plasma was assayed for prolactin, cortisol and growth hormone (GH). Both stressors significantly increased prolactin concentrations over control levels. SCH23390 infusion significantly attenuated the prolactin response to high environmental temperature, but had no effect on the prolactin response to audiovisual stress. Cortisol concentrations were significantly increased by audiovisual stress only and were not affected by SCH23390. GH concentrations were not changed by either stressor or infusion. Drug infusion alone did not affect the concentration of the hormones. The data suggest that the VMH D1 receptors are involved in a prolactin stimulatory pathway in response to high environmental temperature. The inability of the D1 antagonist to affect the response to the barking dog indicates that this pathway is stress-specific, implying that there is more than one mechanism or pathway involved in the prolactin response to different stressors.     

Functional outcome after myocardial revascularization in ischemic left ventricular failure

BACKGROUND: Myocardial revascularization in patients with left ventricular failure (ejection fraction < 30%) offers survival comparable to heart transplantation. The functional outcome, however, has yet to be determined. In order to assess the clinical results in patients with LVEF < 30% undergoing coronary artery bypass grafts (CABG), 101 consecutive patients operated between 1/91 and 1/97 were reviewed retrospectively. METHODS: The patients were stratified according to presentation: 65 pts had angina (Group 1) and 36 congestive failure (Group 2). Mean age (62 +/- 7 vs 60 +/- 8 yrs), sex (90 vs 88% male), LVEF (0.28 +/- 0.04 vs 0.29 +/- 0.04), prior myocardial infarction (1.2 +/- 0.4 vs 1.2 +/- 0.5 episodes/pt), presence of vital myocardium at scintiscan or low-dose dobutamine echocardiography (92 vs 93%), need for preoperative IABP (3.1 vs 8.3%), aortic cross-clamp (53 +/- 21 vs 60 +/- 21 min) and cardiopulmonary bypass (104 +/- 31 vs 114 +/- 36 min) times were comparable. RESULTS: There was only 1 (1%) perioperative death due to low-output syndrome. Eleven pts (6 vs 5, Group 1 vs Group 2) had postoperative low-output syndrome, requiring IABP in 7 pts (4 vs 3). There were 14 (10 vs 4, Group 1 vs Group 2) deaths during follow-up (29 +/- 19 months, range 2-67), with an overall actuarial survival of 91 +/- 4 vs 100% at 1 yr and 74 +/- 9 vs 78 +/- 10% at 5 yrs in Group 1 vs Group 2, respectively (p = ns). Actuarial symptom-free survival was 89 +/- 4 vs 84 +/- 6% at 1 yr and 49 +/- 9 vs 28 +/- 11% at 5 yrs, respectively (p = 0.05). Despite the high recurrence of congestive failure (22 vs 66% in Group 1 vs Group 2, p = 0.004), improvement in functional class (3.1 +/- 0.8 vs 1.5 +/- 0.7 in Group 1 and 2.7 +/- 0.7 vs 1.8 +/- 0.5 in Group 2) and LVEF (0.28 +/- 0.04 vs 0.38 +/- 0.04 in Group 1 and 0.29 +/- 0.04 vs 0.40 +/- 0.06 in Group 2) was found in both groups at follow-up. CONCLUSIONS: In spite of improving early and late survival after revascularization for ischemic left ventricular failure, patients presenting with congestive failure have an unsatisfactory symptom-free survival. Further studies are necessary to ascertain the relative indications to revascularization or transplantation in this specific patient subgroup.     

Purification and characterization of chlorite dismutase: a novel oxygen-generating enzyme

A novel enzyme that catalyzes the disproportionation of chlorite into chloride and oxygen was purified from a gram-negative bacterium, strain GR-1 to homogeneity. A four-step purification procedure comprising Q-Sepharose, hydroxyapatite, and phenyl-Superose chromatography and ultrafiltration resulted in a 13.7-fold purified enzyme with a final specific activity of 2.0 mmol min-1 (mg protein)-1. The dismutase obeyed Michaelis-Menten kinetics. The Vmax and Km calculated for chlorite were 2,200 U (mg protein)-1 and 170 microM, respectively. Dismutase activity was inhibited by hydroxylamine, cyanide, and azide, but not by 3-amino-1,2,4-triazole. Chlorite dismutase had a molecular mass of 140 kDa and consisted of four 32-kDa subunits. The enzyme was red-colored and had a Soret peak at 392 nm. Per subunit, it contained 0.9 molecule of protoheme IX and 0.7 molecule of iron. Chlorite dismutase displayed maxima for activity at pH 6.0 and 30 degrees C.     

Subchronic oral hepatotoxicity of turmeric in mice--histopathological and ultrastructural studies

OBJECTIVE: To analyze the effects of flutamide in patients with physical and/or mental disorders consulting for urinary symptoms secondary to benign prostatic hyperplasia (BPH). METHODS: 50 patients with BPH in whom surgical treatment was contraindicated due to their physical and/or mental condition were treated with flutamide 250 mg/day. Four patients presented with urinary retention and 46 patients had prostatic symptomatology. Patients were evaluated using the symptoms score (I-PSS) and quality of life (QL). Prostate volume was measured by transabdominal US; the maximum flow rate at spontaneous micturition and residual urine were determined. RESULTS: At 12 months, the I-PSS and QL scores decreased by a mean of 7 and 3 points, respectively. The US demonstrated that treatment had reduced prostatic volume by a mean of 10 gms. The maximum flow rate at spontaneous micturition increased 3 ml/sec and residual urine decreased by 15 ml. CONCLUSION: Flutamide is another alternative to surgery in specific patients with BPH.     

Double minutes in the papillary thyroid cancer cell line PTC-1113A

A light microscopy system has been designed for freezing and lyophilization studies of protein pharmaceuticals. The system consists of a cascade of four Peltier thermoelectric modules in the lyophilization cell to freeze samples to -60 degrees C, controllers to regulate temperature and pressure conditions, and a video camera to record the events under study. Specific demonstration of the system was conducted using recombinant CD4-IgG and human growth hormone (hGH) as model proteins. Observations of recrystallization during warming of frozen CD4-IgG solution and lyophilization of hGH solution are discussed. These examples demonstrate that the system is a useful tool for the fundamental understanding of freezing and lyophilization of protein pharmaceuticals.