Pharmacokinetics of aditoprim and trimethoprim in buffalo calves

Pharmacokinetic parameters of two antifolates, trimethoprim and aditoprim, were studied in buffalo calves. The elimination half-life of aditoprim (6.14 h) was nearly twice as long as that of trimethoprim (3.08 h) and compares well with values observed in heifers. This longer half-life of aditoprim is a result of its much larger distribution volume (four to five times larger) because the clearance of aditoprim was about twice as high as that of trimethoprim. The longer half-life of aditoprim is expected to give a longer duration of in vivo bacteriostatic activity than that of trimethoprim.     

Three Cases of Comprehensive Dietary Therapy and Pharmacotherapy of Patients with Complex Obesity-related Diseases

The effect of weight loss with anorectic medications on sleep apnea, non-insulin-dependent diabetes, and steatohepatitis is illustrated in three cases from practice in a clinical nutrition setting. Prevention of obesity, a chronic disorder, is preferable, but when obesity becomes a major obstacle in the care of patients with respiratory, cardiovascular, and metabolic disorders and osteoarthritis, an intense course of weight reduction using anorectic medications under medical and dietetic guidance is essential for patients' survival and reduction of medical cost.     

Delineating the sites and progression of in vivo atrophy in multiple system atrophy using fluid-registered MRI.

We describe the pattern and progression of atrophy delineated using fluid registration of serial magnetic resonance imaging scans in a case of multiple system atrophy (MSA). The in vivo findings were consistent with those found at postmortem, including significant supratentorial atrophy concurrent with an unusual degree of cognitive impairment for MSA.     

Gastric carcinoma--a study of 100 cases in northern Pakistan.

We describe 100 consecutive patients with histologically proven gastric carcinoma who were admitted to various hospitals in Northern Pakistan. Twenty-six per cent of patients were under 40 years of age. In a majority of patients the tumour was of a morphological type associated with poor prognosis. In most cases the disease was already at an advanced stage at the time of diagnosis, and most patients died within one year.     

Brucellosis of the spine

Eight cases of spinal brucellosis are included in this study. Diagnosis was established by positive serology. Back pain was the most common complaint. Functional disturbance in walking was observed in three cases; in two others this was because of impairment of cord function. Clinical hepatosplenomegaly was found in one case. Subclinical organomegaly was diagnosed in two other patients. Psoas abscess was identified by computed tomographic scan in two separate cases. Response to drug therapy and surgical decompression, when indicated, resulted in complete recovery in all patients.     

Cytochrome P450 reductase, antioxidant enzymes and cellular resistance to doxorubicin

Our data suggest that DOX resistance in P388/R-84 cells may result, at least in part, from reduced free radical formation by both suppression of flavin reductase(s) and overexpression of certain antioxidant enzymes such as GSH peroxidase and catalase. In addition, our results, in conjunction with other studies, indicate that flavin reductase(s) and antioxidant enzymes are differentially altered in cancer cells with acquired or de novo resistance to DOX. Further studies are needed, however, to elucidate the mechanism(s) by which the gene expression of these enzymes is regulated in drug-sensitive and -resistant cells.     

Genomic Regions That Underlie Soybean Seed Isoflavone Content

Soy products contain isoflavones (genistein, daidzein, andglycitein) that display biological effects when ingested byhumans and animals, these effects are species, dose and agedependent. Therefore, the content and quality of isoflavones insoybeans is a key to their biological effect. Our objective wasto identify loci that underlie isoflavone content in soybeanseeds. The study involved 100 recombinant inbred lines (RIL) fromthe cross of ‘Essex' by ‘Forrest,' two cultivars that contrastfor isoflavone content. Isoflavone content of seeds from each RILwas determined by high performance liquid chromatography (HPLC).The distribution of isoflavone content was continuous andunimodal. The heritability estimates on a line mean basis were79% for daidzein, 22% for genistein, and 88% for glycitein.Isoflavone content of soybean seeds was compared against 150polymorphic DNA markers in a one-way analysis of variance. Fourgenomic regions were found to be significantly associated withthe isoflavone content of soybean seeds across both locations andyears. Molecular linkage group B1 contained a major QTLunderlying glycitein content (P = 0.0001, R² = 50.2%), linkagegroup N contained a QTL for glycitein (P = 0.0033, R² = 11.1%)and a QTL for daidzein (P = 0.0023, R² = 10.3%) and linkagegroup A1 contained a QTL for daidzein (P = 0.0081, R² = 9.6%).Selection for these chromosomal regions in a marker assistedselection program will allow for the manipulation of amounts andprofiles of isoflavones (genistein, daidzein, and glycitein)content of soybean seeds. In addition, tightly linked markers canbe used in map based cloning of genes associated withisoflavone content.     

Increased production of human immunodeficiency virus (HIV) in HIV-induced syncytia formation: An efficient infection process

Syncytia or multinucleated giant-cell formation is one of the major cytopathic effects induced by human immunodeficiency virus (HIV) infection. Cell fusion results from the strong interaction of CD4 molecules on the surface of the uninfected T cells and gp120, an external envelope glycoprotein of HIV on the infected T cells. We studied the production of HIV in fusion cells between MOLT-4 and virus-infected MOLT-4/HIV cells and found that HIV production was enhanced up to three- to fivefold, which showed a good correlation with the appearance and extent of syncytia formation. Blocking the fusion by monoclonal antibody against a binding epitope of CD4 molecule to gp120 decreased the HIV production significantly. Enhancement of HIV production was observed by more than five-fold in comparison with chronically infected cells, which were fusion free 20 hr postcocultivation. Electron microscopic observation also showed the presence of abundant HIV particles inside the fused cells and on the outer surface. AZT blocked the HIV augmentation of fused cells in coculture completely. Southern blot analysis revealed that both integrated and unintegrated HIV DNA were highly accumulated in fusion cells, as compared with fusion-free MOLT-4/HIV cells. Among unintegrated DNA, circular and linear DNA were accumulated to a similar degree. Northern blot hybridization showed that rapid enhancement of all three species of HIV-specific RNA containing genomic (9.2 kb) and subgenomic (4.3 and 1.9 kb) RNAs were found 20 hr postinfection in fusion cells. These data suggest that syncytia formation is an extremely active infection process of HIV, by which multiple rounds of reinfection might take place.