Effect of insulin treatment on tissue size of the genitourinary tract in BB rats with spontaneously developed and streptozotocin-induced diabetes

To examine the differences between spontaneous and streptozotocin (STZ)-induced diabetes, four parallel studies were performed; three studies of diabetes-prone BB (BBDP/Wor) rats maintained for 8, 16, and 32 weeks and one study of STZ-injected diabetes-resistant BB (BBDR/Wor) rats maintained for 32 weeks. Each diabetic study has three groups of rats: a control group; a euglycemic group, which received sufficient amounts of insulin; and a hyperglycemic group, which received a suboptimal dose of insulin. The extent of tissue weight changes was generally shown to be less dramatic in the euglycemic diabetic than in the hyperglycemic diabetic rats. STZ-induced diabetes increased the bladder weight more dramatically (up to 3-fold) than did spontaneous diabetes (up to 2-fold). Furthermore, a significant decrease in the size of the adrenal gland (20%) and testis (10%) is observed only with spontaneous diabetes, whereas a significant decrease in the size of the ventral prostate (30%) is observed only with STZ-induced diabetes, although the serum testosterone levels are similar in both groups. Our data demonstrate that there are differences in the effect of insulin treatment on the tissue size of the genitourinary tract between spontaneously developed and streptozotocin-induced diabetes in BB rats.     

Predicting proximal femoral strength using structural engineering models

Hip fracture related to osteoporosis and metastatic disease is a major cause of morbidity and mortality. An accurate and precise method of predicting proximal femoral strength and fracture location would be useful for research and clinical studies of hip fracture. The goals of this study were to develop a structural modeling technique that accurately predicts proximal femoral strength; to evaluate the accuracy and precision of this predicted strength on an independent data set; and to evaluate the ability of this technique to predict fracture location. Fresh human cadaveric proximal femora with and without metastatic lesions were studied using computed tomography scan-based three-dimensional structural models and mechanical testing to failure under single-limb stance-type loading. The models understated proximal femoral strength by an average of 444 N, and the precision of the predicted strength was +/- 1900 N. Therefore, the ability to predict hip strength in an individual subject is limited primarily by the level of precision, rather than accuracy. This level of precision is likely to be sufficient for many studies of hip strength. Finally, these models predict fractures involving the subcapital and cervical regions, consistent with most fractures produced experimentally under single-limb stance-type loading.     

Anti-epileptogenic effect of beta-carotene and vitamin A in pentylenetetrazole-kindling model of epilepsy in mice

Vitamin A (Vit A) and its derivatives have recently been reported to be implicated in synaptic plasticity. In this study, the possible effect of Vit A and its precursor, beta-carotene on acute seizure and kindling, induced by pentylenetetrazole (PTZ) was assessed. Vit A and beta-carotene were evaluated for their ability to: (1) elevate the threshold of clonic seizures induced by i.v. infusion of PTZ; (2) suppress the seizures (clonic and tonic) and lethality induced by i.p. PTZ in PTZ-kindled mice (anticonvulsant effect); (3) attenuate the development of sensitization to convulsive and lethal effects of i.p. PTZ in kindled mice (anti-epileptogenic effect). Diazepam was employed as positive control. All the drugs showed anti-epileptogenic effect against PTZ-induced tonic seizures and lethality. Vit A and beta-carotene had no effect on clonic seizures threshold and also on tonic seizures and lethality induced by PTZ in kindled mice. Non-genomic and genomic mechanisms could be involved in the anti-epileptogenic effect of Vit A and beta-carotene.     

Musculoskeletal disorders associated with HIV infection and AIDS. Part II: Non-infectious musculoskeletal conditions

This section of a two-part series on musculoskeletal disorders associated with HIV infection and AIDS reviews the non-infectious musculoskeletal conditions. In the first part, the infectious conditions were reviewed. The non-infectious conditions include polymyositis, drug-induced myopathy, myositis ossificans, adhesive capsulitis, avascular necrosis, bone marrow abnormalities, and hypertrophic osteoarthropathy. Inflammatory and reactive arthropathies are more prevalent in HIV-positive individuals, and a separate section is dedicated to these conditions, including Reiters syndrome, psoriatic arthritis, HIV-associated arthritis, painful articular syndrome, and acute symmetric polyarthritis. Lastly, we include a discussion of HIV-related neoplastic processes that affect the musculoskeletal system, namely Kaposis sarcoma and non-Hodgkins lymphoma.     

Nephrin strands contribute to a porous slit diaphragm scaffold as revealed by electron tomography

Nephrin is a key functional component of the slit diaphragm, the structurally unresolved molecular filter in renal glomerular capillaries. Abnormal nephrin or its absence results in severe proteinuria and loss of the slit diaphragm. The diaphragm is a thin extracellular membrane spanning the approximately 40-nm-wide filtration slit between podocyte foot processes covering the capillary surface. Using electron tomography, we show that the slit diaphragm comprises a network of winding molecular strands with pores the same size as or smaller than albumin molecules, as demonstrated in humans, rats, and mice. In the network, which is occasionally stratified, immunogold-nephrin antibodies labeled individually detectable globular cross strands, about 35 nm in length, lining the lateral elongated pores. The cross strands, emanating from both sides of the slit, contacted at the slit center but had free distal endings. Shorter strands associated with the cross strands were observed at their base. Immunolabeling of recombinant nephrin molecules on transfected cells and in vitrified solution corroborated the findings in kidney. Nephrin-deficient proteinuric patients with Finnish-type congenital nephrosis and nephrin-knockout mice had only narrow filtration slits that lacked the slit diaphragm network and the 35-nm-long strands but contained shorter molecular structures. The results suggest the direct involvement of nephrin molecules in constituting the macromolecule-retaining slit diaphragm and its pores.     

Methadone versus buprenorphine maintenance for the treatment of heroin-dependent outpatients

The aim of this study was to assess the efficacy of methadone compared with buprenorphine maintenance therapy in heroin-dependent patients over a treatment period of 18 weeks. Subjects were randomized to receive either methadone or buprenorphine in a comparative double-blind study and consisted of 164 heroin-dependent male patients who met the DSM-IV criteria for heroin dependence and were seeking treatment. The 164 subjects included 41 patients in 1-mg, 41 patients in 3-mg, and 41 patients in 8-mg dosage group of buprenorphine, and also 41 patients in the 30-mg dosage group of methadone. The mean age was 31.4 years for total buprenorphine group and 33.7 years for methadone group (the mean age differences in 4 groups were not statistically significant). Subjects received buprenorphine at a dose of 1, 3, or 8 mg per day or methadone at a dose of 30 mg per day and were treated in an urban outpatient clinic, offering a 1-hour weekly individual counseling session. Days retained in treatment were measured. Completion rates by buprenorphine dosage group were 29.3% for the 1-mg dose group, 46.3% for the 3-mg dose group, 68.3% for the 8-mg dose group, and 61% for the 30-mg methadone dose group. Retention in the 8-mg dose group was significantly better than in the 1-mg dose group (p=.00041) and in the 3-mg dose group (p=.045); other comparison (1 mg dose with 3 mg dose) was not significant. Methadone group was significantly better than 1mg buprenorphine dose group (p=.004), but was not significantly different from 3 mg buprenorphine dose group (p=.18) or 8 mg buprenorphine dose group (p=.49). The results support the efficacy of buprenorphine for outpatient treatment of heroin dependence and seem to indicate that the highest dose (8 mg) of buprenorphine was the best of the three doses of buprenorphine, and also support the superiority of 30 mg of methadone compared to 1 mg dose of buprenorphine for Iranian heroin-dependent patients to increase their retention in treatment.     

Pathology of brain parenchyna in meningeal carcinomatosis; Immunohistochemical study with astroprotein (GFAP) and tubulin

Effects of leptomeningeal tumor on the brain parenchyma was studied by the immunohistochemical method with astroprotein (GFAP) and tubulin in a rat model of meningeal carcinomatosis. Thickening of subpial glial lining (external glial layer) and hypertrophy of subpial astrocytes, detected by the antiserum to GFAP, was the early sign of parenchymal involvement. The glial lining was continuous as far as the tumor cells were confined to the subarachnoid space, however, penetration of tumor cells into subpial brain was associated with disruption of the glial lining. Speculative role of this lining in preventing the tumor cell to infiltrate into brain tissue was discussed. In contrast to the prominent immunohistochemical changes in astrocytes, neuronal tubulin immunoreactivity was not altered even in the late stage of the disease. The present study demonstrated that the leptomeningeal dissemination of tumor cells did cause pathologic change in brain parenchyma as was evidenced by the reactive change of astrocytes. However, the preserved immunoreaction for tubulin suggested that the nerve cell damage was not severe even at the advanced stage of the disease. address for offprints