Inhibition of canine lung angiotensin converting enzyme by substance P

We have studied inhibition of purified canine angiotensin converting enzyme by substance P and its nonapeptide derivative using Hip-His-Leu as the substrate. Kinetic studies indicated that both substance P and its nonapeptide derivative inhibited the hydrolysis of Hip-His-Leu at different concentrations. The mode of inhibition was competitive with a Ki of 1.15 microM for substance P. These results indicate that substance P is a potent inhibitor of angiotensin converting enzyme in vitro.     

Modifications of primaquine as antimalarials. 1. 5-Phenoxy derivatives of primaquine.

Various 5-phenoxy derivatives of primaquine have been prepared which are more active and less toxic than the parent compound in murine and monkey antimalarial screens. An improved method for the phthalimido alkylation of amines is described.     

Human chromosome heteromorphisms in American blacks: II. Higher incidence of pericentric inversions of secondary constriction regions (h)

Eighty normal American blacks were studied by the CBG technique (C-bands by barium hydroxide using Giemsa) for estimation of size and inversion heteromorphisms of chromosomes 1, 9, and 16, and the data were compared to those of whites using subjectively defined criteria. Size and inversion heteromorphisms were classified into 5 levels. The frequencies of size heteromorphisms of chromosomes 1 and 16 were 10.63% and 6.88%, respectively, which are not significantly different from those of a normal population of whites. A higher incidence of size heteromorphisms for chromosome 9 was noted in whites (47.5% vs 30%). The frequencies of inversion heteromorphism of chromosomes 1, 9, and 16 were 17.5%, 21.9%, and 0.0%, respectively. Overall, 61 chromosomes were found to have an inversion. Of these, 28 were in chromosome 1, and 33 were in chromosome 9. A higher incidence of inversion heteromorphisms of chromosomes 1 and 9 was noted in American blacks, while no inversions were found in chromosome 16 in either population. A significant association of increased size of the h region with inversion (r = 0.99 P < 0.01) is demonstrated, ie, enlarged h regions have a higher frequency of inversions.     

Pesticide-induced alterations in the oxygen uptake rate of a freshwater major carp Labeo rohita

In one of the series of experiments, regular oxygen consumption (VO₂) was determined in six continuous-flow respirometers in water containing different concentrations of pesticides, i.e., chlordane (organochlorine), Metasystox (organophosphorus), and Sevin (carbamate). The concentrations which were selected for the experiment were 1, , , , and of the TL₅₀ values of each pesticide and VO₂ was determined after intervals of 2, 4, 6, 8, 10, 12, 24, 36, 48, 60, 72, 84, and 96 hr. At the TL₅₀ values of the pesticides an all or none response was observed, but at all other concentrations the period of VO₂ was observed in three different but clear phases: (a) sensitization phase (b) responsive phase; and (c) normalization phase. Every said phase has shown marked differential persistence for different time periods probably depending on the different concentrations of the pesticides used in experiment. Further the oxygen uptake data show that in general there is a critical threshold time for the hyperactivity response: between 6 and 24 hr for chlordane; from the very beginning up to 6 hr for Metasystox, and between 2 and 24 hr for Sevin. It was also noted that animals which took the longest time to show the hyperactive response exhibited the lower initial rates of VO₂. Hence it is axiomatic that respiratory changes are good indicators of environmental stressors.     

Measuring children and monitoring obesity: surveys of English Primary Care Trusts 2004-06

BACKGROUND: Child obesity has unclear determinants and consequences. A precautionary approach requires best-guess interventions and large-scale surveillance. This study was to determine the current measurement activities and the information systems required for child obesity surveillance. METHODS: DESIGN: Questionnaire-based surveys. SETTING: Primary Care Trusts (PCTs) in United Kingdom. PARTICIPANTS: Two hundred and forty-seven (82%) PCTs in 2004 and 240 (79%) in 2006. MAIN MEASURES: Children's ages at which height and weight are routinely measured, the type of personnel taking the measurements, arrangements for recording data, information systems and uses of the data. RESULTS: PCTs measure height/length and weight most commonly at 6 weeks (74%) and 5 years (74%)-also at 6-12 months (58%), 1.5-2.5 years (50%), 2.5-4 years (40%), 11 years (18%) and 7 years (11%). Seventy-seven per cent of PCTs transferred the measurements to a database-26 different information systems were named. Six per cent of PCTs in 2004, rising to 34% in 2006, used the data to produce public health reports. CONCLUSIONS: Body mass index (BMI) surveillance requires new arrangements in 25% of PCTs at school entry and 80% at transfer to senior school. Important aspects of child obesity surveillance not yet addressed are pre-school measurement, longitudinal assessment and the public health requirements of (child) electronic health records.     

The L-type calcium channel blocker nimodipine mitigates cytoskeletal proteins phosphorylation in dichlorvos-induced delayed neurotoxicity in rats

The present investigation was carried out to assess the protective efficacy of nimodipine against dichlorvos-induced organophosphate induced delayed neurotoxicity (OPIDN). Single subcutaneous dose of dichlorvos (200 mg/kg body weight) led to a consistent increase in the activity of both microtubule associated protein kinases viz. Ca2+/Calmodulin-dependent and cAMP dependent protein kinases, at all post exposure intervals (day 7, 15 and 21) as compared to that of controls. Autoradiography followed by microdensitometric studies demonstrated enhanced phosphorylation of 55 kDa and 280 kDa proteins in dichlorvos-exposed animals. These two proteins were confirmed to be tubulin and microtubule associated protein-2 (MAP-2) by western blotting. The hyperphosphorylation of these two proteins was shown to interfere with the assembly of neuronal microtubules as shown by electron microscopic studies that may eventually lead to possible disruption of neuronal cytoarchtecture resulting in axonal degeneration. Administration of nimodipine along with dichlorvos brought about a significant reduction in the activities of both the kinases as well as the extent of microtubule associated protein phosphorylation. This indicates that nimodipine, a centrally acting calcium channel blocker, may contribute to the amelioration of dichlorvos induced neurotoxicity by attenuation of calcium mediated disruption of cytoskeletal proteins and hence, calcium channel blockers like nimodipine have great future as new therapeutic agents for OPIDN.     

FDG-PET after 1 cycle of therapy predicts outcome in diffuse large cell lymphoma and classic Hodgkin disease

BACKGROUND: Early prediction of response to therapy may offer the potential to identify patients who will benefit from standard conventional therapy. The objective of this study was to determine the predictive value of FDG-PET as an early response indicator after 1 cycle of chemotherapy for progression-free survival (PFS) in diffuse large cell lymphoma (DLCL) and classic Hodgkin disease (HD). METHODS: FDG-PET was performed before, after 1 cycle, and after completion of chemotherapy in 47 patients. The patients were followed with a median follow-up of 21 months (range, 3-47 months). PFS was compared between PET-positive and PET-negative patients after 1 cycle and after completion of therapy. RESULTS: All PET-negative patients after 1 cycle (n = 31) had sustained complete remission with a median follow-up of 28 months. Fourteen of 16 PET-positive patients after 1 cycle had refractory disease or relapsed (median PFS, 5.5 months). There were 2 false-positive results, 1 with an active infection at the biopsy site and the other in a patient who had been in remission after radiation therapy. There was good agreement between the results obtained after 1 cycle and at completion of therapy (kappa, 0.80); however, the negative predictive value was higher for FDG-PET after 1 cycle than after completion of chemotherapy (100% vs 91.4%), although not statistically different (P = .40). CONCLUSIONS: FDG-PET had a high prognostic value after 1 cycle of chemotherapy, thus it can be a valid alternative for posttreatment evaluation of DLCL and HD and may offer the potential for change in treatment paradigms.