Acute and chronic effects of cisplatinum upon testicular function in the rat

One of the side effects of cisplatinum-based chemotherapy is the impairment of spermatogenic function. In order to understand the mechanisms responsible for this side effect, the present study examined the short- and long-term effects of five daily injections of 2 mg/kg cisplatinum upon the functional normality of Leydig cells and Sertoli cells in intact adult rats, and their relationship with the status of spermatogenesis. Results of the present study demonstrate that cisplatinum treatment resulted in a progressive but reversible loss of germ cells from the seminiferous epithelium. Although testicular testosterone contents reduced transiently after the adminisration of cisplatinum, these testosterone levels are otherwise sufficient to support complete spermatogenesis. Thus, the cisplatinum-induced germinal regression cannot be accounted for by hypoandrogenism. The testicular ABP contents of the drug-treated rats remained unchanged during the treatment period, decreased transiently 30 days after the treatment, and returned to normal 120 days after treatment. A decrease in epididymal ABP content was also noted 10 and 30 days after the drug treatment. These observations suggest that Sertoli cell functions were affected by cisplatinum treatment. The effects of cisplatinum upon Sertoli cells were further demonstrated by the dose-dependent suppression of the production of ABP, lactate, and estradiol in cultured Sertoli cells. In addition, cisplatinum administration resulted in a reversible decrease in pituitary weights and an irreversible decrease in seminal vesicle weights. These results further demonstrate the toxic effects of cisplatinum upon various aspects of the male reproductive system.     

Posterior Cervical-Thoracic Thermograms: Pattern Persistence and Correlation with Chronic Headache Syndromes

SYNOPSIS
These experiments investigate thermographic patterns in the posterior cervical/thoracic (PCT) region of 530headache patients and 30 headache/injury-free volunteers. The study examines: The longitudinal persistence ofProximal and Distal patterns; three distinct midline patterns (PCT I, II, and III); and their correlation with diagnosis,injury, and pain.
Twenty-four (80%) of 30 randomly selected subjects displayed unchanged Proximal patterns at the meanobservation period of 5.5 months. PCT pattern fluctuations occurred in 13/30 (43.3%) subjects. The distinctivenessof each subject's Proximal and Distal patterns was verified by blind calling of thermogram pairs. Patternpersistence was validated with alcohol spray-Patterns were identical regardless of using a 0.5°C or 1.0°Ctemperature setting. Temperature settings of 1.0°C yielded more distinct Proximal and Distal patterns.
Chi square analysis determined that there was no significant difference in the number of PCT III patterns in theexperimental or control groups.
In conclusion, it appears that Proximal and Distal Patterns may be consistent over time and individually unique,but that PCT patterns fluctuate and, therefore, do not correlate with chronic headaches.     

Ziprasidone, Diazepam, or the Combination for Prevention of Cocaine Toxicity in a Mouse Model

Background Acute cocaine poisoning is a common problem in the United States. Sedation with benzodiazepines is the standard treatment, but animal studies have suggested that ziprasidone is also protective.
Objectives To assess whether the combination of these two medications would offer more protection than either treatment alone.
Methods This was a randomized, blinded, placebo-controlled trial in CF-1 mice. The authors administered intraperitoneal injections of 2 mg/kg diazepam (group D), 4 mg/kg ziprasidone (group Z), the same dose of both drugs (group DZ), or saline 15 minutes before intraperitoneal administration of 105 mg/kg cocaine (an estimated lethal dose to 70%). The number of animals with seizures and apparent lethality over the following 30 minutes was recorded.
Results All treatments increased survival relative to placebo (relative risk: D = 2.6, Z = 2.3, DZ = 2.9) and decreased seizures (relative risk: D = 0.5, Z = 0.3, DZ = 0.02).
Conclusions This study suggests that diazepam and ziprasidone have efficacy for preventing lethality from cocaine poisoning in an animal model but that the combination offers little addition to either therapy alone. However, the combination may be more effective for prevention of cocaine-induced seizures.     

Effect of once-daily fluticasone furoate nasal spray on nasal symptoms in adults and adolescents with perennial allergic rhinitis.

BACKGROUND: Intranasal corticosteroids are recommended as first-line therapy for the treatment of allergic rhinitis. Fluticasone furoate is a novel enhanced-affinity glucocorticoid for the treatment of allergic rhinitis. OBJECTIVE: To compare the efficacy and safety of intranasal fluticasone furoate with those of vehicle placebo nasal spray in adult and adolescent patients with perennial allergic rhinitis (PAR). METHODS: After screening (7-14 days), patients 12 years and older with confirmed PAR were randomized to receive fluticasone furoate, 110 microg once daily, or placebo once daily intranasally for 4 weeks in this double-blind, multicenter study. The primary end point was mean change from baseline during the entire treatment period in daily reflective total nasal symptom score (rTNSS), recorded on diary cards by patients, using a 4-point categorical scale. RESULTS: The mean reduction from baseline during the treatment period in daily rTNSS was significantly greater in fluticasone furoate recipients than in placebo recipients (P = .005). This finding was supported by significantly greater mean reductions in morning rTNSS and evening rTNSS (P = .004 and P = .011, respectively). A significantly greater mean reduction in instantaneous morning predose TNSS with fluticasone furoate compared with placebo (P = .006) confirmed the efficacy of once-daily administration. Fluticasone furoate was also significantly more effective than placebo in overall response to therapy (P = .005). CONCLUSIONS: Fluticasone furoate nasal spray, 110 microg once daily, effectively relieved nasal symptoms of PAR in adults and adolescents 12 years and older.     

An analysis of myeloma plasma cell phenotype using antibodies defined at the IIIrd International Workshop on Human Leucocyte Differentiation Antigens.

Fresh bone marrow from 43 cases of myeloma and three cases of plasma cell leukaemia has been phenotyped both by indirect immune-rosetting and, on fixed cytospin preparations, by indirect immunofluorescence. Both clustered and unclustered B cell associated antibodies from the IIIrd International Workshop on Human Leucocyte Differentiation Antigens were used. The results confirm the lack of many pan-B antigens on the surface of myeloma plasma cells, i.e. CD19-23, 37, 39, w40. Strong surface reactivity is seen with CD38 antibodies and with one CD24 antibody (HB8). Weak reactions are sometimes obtained with CD9, 10 and 45R. On cytospin preparations CD37, 39 and w40 are sometimes weakly positive, and anti-rough endoplasmic reticulum antibodies are always strongly positive. Specific and surface-reacting antiplasma cell antibodies are still lacking.     

The immune response in steroid deficient mice

Adrenalectomy, gonadectomy and combined adrenalectomy—gonadectomy resulted in increased spleen weights, spleen cell counts and 19S plaque-forming cells following primary and secondary immunization of mice with SRBC when compared to controls. Plaque-forming cells of the 7S type in the spleen did not increase when measured on the eleventh day following the primary or the third day following secondary sensitization. Combined adrenalectomy—gonadectomy had a greater effect on spleen cell counts, spleen weights and plaque-forming cells in the primary and secondary response than either operation alone. Haemolysin titres were not significantly different between test and sham operated animals in the primary and secondary responses.

In the primary responses, it appears that the increase in spleen weight and cell count is responsible for the increase in 19S plaque-forming cells. The response to a second injection of SRBC demonstrated that 19S antibody-producing cells increased three-fold in steroid depleted mice above the control values. In the test animals the 19S antibody-producing cells of the spleen were relatively enriched above that of the controls.