Changes in membrane-bound hydrolases by metronidazole in rat renal brush border

The antiprotozoal drug metronidazole, when administered orally at a dose level of 100 mg/kg body wt. daily for 7 days to rats, brought about significant elevation of renal brush-border-membrane-bound hydrolytic enzymes, such as alkaline phosphatase, maltase, sucrase, and leucine aminopeptidase (LAP). Kinetic analysis of the enzymes (substrate saturation) indicated that the drug produced an increase in the maximum of apparent initial enzyme velocity (Vmax), while the substrate affinity constant (Km) remained unaltered. These changes were not recovered to the normal level even after the drug regimen was stopped and the animals were allowed to recover for a period of 7 days. Lipid analysis of brush border membrane (BBM) revealed a significant elevation in the cholesterol, phospholipid, and ganglioside levels, while no marked change was recorded in triglyceride, free fatty acid and plasmalogen. Study of the temperature-dependent parameters of the enzymes showed that metronidazole induced a shift in the transition temperature (To) in LAP with nearly total reversibility in the recovery group. No such change was seen in the other enzymes. However, there also was a lowering in the energy of activation (Ea) below To, which returned to normal after the treatment was withdrawn.     

The transformation of acute viral hepatitis B into chronic

500 patients with hepatitis B have been followed up from the acute onset to long-term outcome. As for chronic transformation of the disease, at higher risk are patients with mild form, progredient run and inadequate immune response. Of the highest value for identification and prognostication was a dynamic quantitative control over the system HBeAg-anti-HBe providing separate prognosis of establishment of replicative or integrative variants of chronic hepatitis B. In progredient infection an early administration of reaferon in combination with thymogen is thought valid which in many patients is sufficient to prevent the disease transformation into a chronic form.     

Adjuvant immunotoxin therapy with anti-B4-blocked ricin after autologous bone marrow transplantation for patients with B-cell non-Hodgkin's lymphoma

Anti-B-blocked ricin (anti-B4-bR) combines the specificity of the anti-B4 (CD19) monoclonal antibody with the protein toxin "blocked ricin." In blocked ricin, affinity ligands are attached to the ricin B-chain to attenuate its lectin binding capacity. In a phase I trial, Anti-B4-bR was administered by 7-day continuous infusion to 12 patients in complete remission after autologous bone marrow transplantation (ABMT) for relapsed B-cell non-Hodgkin's lymphoma (NHL). Patients were treated at 20, 40, and 50 micrograms/kg/d for 7 days. Potentially therapeutic serum levels could be sustained for 3 to 4 days. The maximum tolerated dose was 40 micrograms/kg/d for 7 days (total 280 micrograms/kg). The dose-limiting toxicities were reversible grade IV thrombocytopenia and elevation of hepatic transaminases. Mild capillary leak syndrome was manifested by hypoalbuminemia, peripheral edema (4 patients), and dyspnea (1 patient). Anti-immunotoxin antibodies developed in 7 patients. Eleven patients remain in complete remission between 13 and 26 months post-ABMT (median 17 months). These results show that Anti-B4-bR can be administered with tolerable, reversible toxicities to patients with B-cell NHL in complete remission following ABMT.     

Phosphate fertilization in intensive annual cropping with wheatgreen gram (or cowpea) — pearl millet

In a four year study on a wheat-green gram (or cowpea) — pearl millet intensive cropping system a total production of 9–10 tonnes of wheat equivalents per year removed 29–30kg P ha^–1. If only 26 kg P ha^–1 was used then total grain production as well as P uptake, was highest when all the P was applied to wheat. Only when amounts larger than 26 kg P ha^–1 were applied was it justified to apply P to pearl millet and green gram (or cowpea). Productivity of the cropping system increased up to 58.5 kg P ha^–1 and at this level two thirds of P was applied to wheat, while pearl millet and green gram or cowpea received the remaining one-third. A positive P balance in soil was observed only when 26 k P ha^–1 yr^–1 or more was applied.Pressure of growing population and per capita diminution or arable land has focussed attention on multiple cropping systems in many Asian countries [1, 2]. In North-Western India the cropping system changed from a single rainy (July–October) or winter (November–April) crop a year prior to the 1960's to two-crops-a-year (both a rainy season and winter crop) in the 1970.s and then in the late 1970's a third summer (May–June) crop was also included. Wheat — green gram (or cowpea) — pearl millet is such a three-crops-a-year multiple cropping system.Phosphate is the costliest major plant nutrient in India and farmers following multiple cropping systems are keen to know the way the phosphate should be apportioned to different crops in a cropping system particularly when small amounts of P are applied. Such information can come only from long-term P fertilization experiments [3, 4]. The objective of the present experiment on a wheat-green gram (or cowpea) — pearl millet multiple cropping system was to study the direct and residual effects of P applied to one crop on the other crops grown in succession and to find the best possible way in which a limited amount of P could be apportioned between the different crops in the rotation. An attempt has also been made to work out the P balance in soil.     

An investigation of the intrinsic circuitry of the motor cortex of the monkey using intra-cortical microstimulation

Community support programs are increasingly establishing paid service positions designated exclusively for consumers. Project WINS (Work Incentives and Needs Study), a hybrid case management-vocational program for individuals with severe mental illness, used consumers as peer support specialists (PSSs) to supplement professional roles. Semistructured interviews were conducted with PSSs about 12 months after their employment ended. They identified substantial personal benefits specific to consumer-designated roles (e.g., a "safe" employment setting with accommodations) and general benefits from employment. Problems described were just as numerous, encompassing attitudes toward assigned peers and costs to their own well-being. Critical commentary addressed program operations (structure, supervision, and training needs) and problems in the mental health system. The authors discuss the changed sense of self that service provider roles can create for consumers and suggest that mental health administrators provide anticipatory socialization for this service innovation throughout their agencies and ongoing supports for consumers in their new roles.     

Metabotropic glutamate receptors are involved in calcium-induced LTP of AMPA and NMDA receptor-mediated responses in the rat hippocampus

INTRODUCTION: Previous studies have demonstrated a high prevalence of "white coat" hypertension (20%), but it is still controversial if it implies an increase in cardiovascular risk. PATIENTS: Between 1992 and 95 we prospectively studied 175 untreated hypertensive patients aged over 18 years (V Joint National Committee's stage I-II), and 91 controls. DESIGN AND METHODS: The subjects were submitted to clinical evaluation, ambulatory blood pressure monitoring, 24-hour Holter monitoring, signal-averaged ECG, echocardiography/Doppler and ergometry. "White coat" hypertension was defined as mean daytime (6.00-22.00 H) ambulatory blood pressure < 136/87 mm Hg (males) and < 131/86 mm Hg (females). RESULTS: "White coat" hypertension was present in 29 patients (18%). "White coat" hypertension patients had an identical prevalence of smoking, family history of cardiovascular disease, abnormal ECG and retinopathy (> Keith-Wagener II) as patients with daytime hypertension. Ambulatory blood pressure values (24 hour, 6.00-22.00 h, 22.00-6.00 h, sleep, blood pressure load, heart rate) were all significantly different from controls (p < 0.03 to 0.0007). In patients with daytime hypertension, only 24 hour and daytime diastolic ambulatory blood pressure (p < 0.005) were different from "white coat" hypertension patients. Exercise testing blood pressure values (6 min exercise, maximal, 3 min recovery) were significantly different between "white coat" hypertension patients and the control group (n = 70) (p varying from 0.05 to 0.005) but not between "white coat" hypertension and daytime hypertension (n = 33) patients. Diastolic function was studied only in 39 daytime hypertension patients, 10 individuals with "white coat" hypertension and 34 controls (for technical reasons and because we only analyzed individuals younger than 55 years). E velocity and E/A ratio were similar in "white coat" hypertension and daytime hypertension, but only in daytime hypertension patients they reached a significant difference from controls (p = 0.04; p = 0.01), probably due to the small number of patients. CONCLUSIONS: These data (clinical, ambulatory blood pressure, ergometric, diastolic function) suggest that "white coat" hypertension might not be a benign entity.     

Considering the role of the amygdala in psychotic illness: a clinicopathological correlation

Today a "just" health policy is balanced between the problem of the allocation of scarce resources and the priority setting of services, care and cures. Despite technologies and molecular medicine, with their tendency to reach absolute prediction of disease or absence of disease and to cure with predicted efficacy, a large portion of the public refuse the results of experimental procedures and prefer to place trust in so-called alternative medicine or in drugs which are not in the official guide-lines following the principles of evidence-based medicine according to DL Sackett. Juridical problems arise between the rights of free choice of cure and social dimension of Governmental care programs, which include the maximum of benefits (i.e. effective therapies) for a pre-fixed total budget. An explicit rationing only on budgetary bases without rationalisation of medical procedures reduces the rights to care of citizens-patients. Thus, an explicit rationing-rationalisation seems to be the only procedure compatible with the interest of patients in a social security system allocating "scarce" resources.