The effects of pentoxifylline on skeletal muscle contractility and neuromuscular transmission during hypoxia

Objectives:

The objective of this study was to investigate the effects of pentoxifylline (PTX), a drug that is mainly used for indications related to tissue hypoxia, on hypoxia-induced inhibition of skeletal muscle contractility and neuromuscular transmission in mice. We hypothesized that chronic PTX treatment alters skeletal muscle contractility and hypoxia-induced dysfunction.

Materials and Methods:

Mice were treated with 50 mg/kg PTX or saline intraperitoneally for a week. Following ether anesthesia, diaphragm muscles were removed; isometric muscle contractions and action potentials were recorded. Time to reach neuromuscular blockade and the rate of recovery of muscle contractility were assessed during hypoxia and re-oxygenation.

Results:

The PTX group displayed 90% greater twitch amplitudes (P < 0.01). Hypoxia depressed twitch contractions and caused neuromuscular blockade in both groups. However, neuromuscular blockade occurred earlier in PTX-treated animals (P < 0.05). Muscle contractures developed during hypoxia were more pronounced in the PTX group (P < 0.05). Re-oxygenation reduced contracture and indirect muscle contractions resumed. The rate of recovery of contractions was faster (P < 0.05) and the amplitude of contractions was greater (P < 0.01) in the PTX group. PTX treatment increased amplitude (P < 0.05) and shortened action potential (P < 0.05) without altering resting membrane potential, excitation threshold, and neurotransmitter release.

Conclusion:

Chronic PTX treatment increases diaphragm contractility, but amplifies hypoxia-induced contractile dysfunction in mice. These results may implicate important clinical consequences for clinical usage of PTX in hypoxia-related conditions.     

Musculoskeletal manifestations of Russell-Silver syndrome

The musculoskeletal manifestations of Russell-Silver syndrome were studied in 25 patients. The most common manifestations were short stature (25 patients), limb-length discrepancy (23 patients), clinodactyly (19 patients) metacarpal bone and phalangeal abnormalities (13 patients), scoliosis (9 patients), foot syndactylism (5 patients), and developmental dysplasia of the hips (3 patients). Five patients underwent lower extremity limb-lengthening procedures for discrepancies greater than 3 cm and three patients had successful pelvic and/or femoral osteotomies for hip dysplasia. All 18 patients studied had retardation of bone age, which peaked at age 7 years.     

Transphyseal osteotomy of the distal tibia for correction of valgus/varus deformities of the ankle

This study is a retrospective review of the results of consecutive cases of a transphyseal osteotomy of the distal tibia. Indications for the procedure are significant valgus or varus deformities of the ankle needing acute correction because of problems with the skin and brace fit as well as progressive deformity. Twenty-one patients with a variety of underlying diagnoses, five with bilateral deformities, underwent this procedure. The technique involved making either a medially based closing or opening wedge with the distal limb of the osteotomy through the physis or the physeal scar so that it was very close to the ankle joint. A fibular osteotomy was not necessary except in three ankles. All osteotomies healed. All patients were able to ambulate and use their braces as soon as their osteotomies healed, and none had any further pressure sores or brace-related problems, although some had mild residual valgus or varus deformities. There were no significant leg-length discrepancy problems as a result of the surgery. This osteotomy is a treatment alternative for significant angular deformities of the ankle that require acute correction.     

Is stress urinary incontinence a familial condition?

BACKGROUND: Stress urinary incontinence (SUI) is a common problem of multifactorial origin. Some authors have claimed that it has a familial predisposition. This study was undertaken to investigate the prevalence of SUI among first-degree relatives of 154 women who had been operated on for this disorder and of 100 women without SUI. METHODS: This report is concerned with a questionnaire-based, case-control study. A total of 154 women who had undergone operations for SUI and 100 women who denied having SUI were included. A comparison was made of 413 first-degree relatives of incontinent women and 372 first-degree relatives of continent women according to the demographic characteristics, obstetric and gynecologic history and risk factors for SUI. The prevalence of SUI was investigated among the relatives. Furthermore, the characteristics of the women who had SUI operation were compared according to the continence state of their families. RESULTS: The prevalence of SUI was 71.4% among mothers and 24.6% among sisters of operated women compared with 40.3% among mothers and 11.6% among sisters of continent women (p < 0.05). Furthermore, the age at which symptoms began was significantly lower in the members of the 'incontinent families' (p < 0.001). CONCLUSIONS: The relatives of incontinent women displayed a higher prevalence of SUI than the relatives of continent women. Although this condition has a multifactorial origin, the familial aggregation of SUI and the appearance of symptoms at younger ages in women with a family history of SUI suggest that heredity may play a significant role.     

Influence of viral load and alanine aminotransferase on viral genetic heterogeneity in patients with chronic hepatitis C virus infection

BACKGROUND/AIM: Hepatitis C virus (HCV) populations in vivo consist of genetically different heterogeneous mixtures defined as 'quasispecies', which vary in the hypervariable region 1 (HVR1) mostly. To further address the role of quasispecies diversity in hepatitis C infection, this study aimed to evaluate the influence of ALT, viral load and genotypes on quasispecies heterogeneity in patients with HCV infection. METHODS: Thirty-six chronic hepatitis C patients with high levels of alanine aminotransferase (ALT) were studied. None of them received any antiviral therapy. HCV RNA serum levels, genotype and genetic heterogeneity were determined by branched-chain DNA assay, restriction fragment length patterns and RT-PCR single-strand conformational polymorphism analysis of HVR1, respectively. RESULTS: Twenty-eight patients had genotype 1b (28/36; 78%), 6 patients had genotype 1a (6/36; 17%), 1 patient was 2a (1/36; 3%) and genotype could not be determined in 1 patient. The patients were categorized into two groups according to the number of bands representing the dominant strains in the circulation: group A with 2 bands having 1 strain (14/36 patients; 39%) and group B with more than 2 bands indicating more than 1 strain (22/36 patients; 61%). The serum viremia and ALT levels for these groups were 11 +/- 8.8 and 5.3 +/- 4.6 mEq/ml (p < 0.05), and 79 +/- 20, and 127 +/- 80 IU/l (p < 0.05), respectively. CONCLUSION: The results of this study suggest that hepatitis C patients having 1 dominant strain in the circulation may show a relatively weaker immune response resulting in lower ALT and higher viremia levels, whereas patients with high degrees of virus quasispecies diversity have higher ALT levels and a more active immune response causing the selection of new genome variants and depressing viral replication partly.     

Modulating interaction of glutathione-S-transferase polymorphisms with smoking in endometriosis

OBJECTIVE: To evaluate the interaction of glutathione-S-transferase (GST) gene polymorphisms and smoking as a risk factor for endometriosis. STUDY DESIGN: The study group consisted of 150 women who were diagnosed by means of surgery and histopathology as having endometriosis. The control group consisted of 150 women who displayed no evidence of endometriosis during exploratory laparotomy or laparoscopy. We assessed the interaction of smoking and GSTM1 and GSTT1 polymorphisms in these patients. RESULTS: Logistic regression analyses showed that the GSTM1-null allele was associated with a significantly increased risk of endometriosis and smoking with a decreased risk of endometriosis separately. There was no association between endometriosis and the GSTT1-null allele. The interaction of smoking and GST polymorphisms showed a joint effect. We found that the GSTM1-null allele was more prevalent in active smoking endometriosis patients (63.4%) than in the controls (35.0%), and the difference was statistically significant. A similar tendency was also observed in the GSTT1 allele distribution. CONCLUSION: Genetic factors could modify the response to environmental pollutants in endometriosis.     

Estradiol induces JNK-dependent apoptosis in glioblastoma cells

Estrogens exert multiple regulatory actions on cellular events in a variety of tissues including the brain. In the present study, the signaling mechanisms of the concentration-dependent effects of 17-β-estradiol (estradiol) on glioblastoma cells were investigated. Cell viability was evaluated by the trypan blue exclusion assay. Cell growth and kinase activities were evaluated by immunocytochemistry and Western blotting. The results showed that high concentrations of estradiol inhibit growth and induce apoptosis in C6 rat glioma and T98G human glioblastoma cells. The blockade of the c-jun NH(2)-terminal kinase (JNK) signaling pathway prevented these effects of estradiol, indicating the critical role of the JNK/c-jun signaling cascade in glioblastoma cell growth inhibition and cell death in response to high concentrations of estradiol. Collectively, these findings highlight the potential of new discoveries in sensitizing estrogen-sensitive tumors to chemotherapeutic drugs, and may lead to the development of new JNK-based effective therapies.