Physico-Chemical Characterization of the Soluble 3α-Hydroxysteroid Oxidoreductase in the Rat Testis and Prostate

The present paper describes some physicochemical properties of the soluble 3α-oxidoreductases in the rat testis and prostate, and comparison with rat epididymal 3α-oxidoreductase, published previously (Hastings & Hansson 1979). The testicular enzyme shows properties very similar to that in the epididymis (size, stability, pH optium) except for minor differences in charge (iso-electric point). The prostatic enzyme revealed a slightly higher molecular weight, and was more sensitive to heating than those in the testis and epididymis, whereas the iso-electric point was the same as that in the testis (pI-5.25). The enzymes in all tissues exhibit very similar shapes (f/fo 1.14-1.17).
The similar properties of the testicular and prostate 3α-oxidoreductases to those previously reported for that in the epididymis may indicate that these enzymes represent identical peptide chains. The small differences observed in size, temperature stability and change may be due to their presence in different environments.     

Blood platelet count and reactivity are associated with restenosis 6 months after coronary angioplasty

OBJECTIVES: Restenosis occurs in 40-50% of patients treated with percutaneous transluminal coronary angioplasty (PTCA). Some data indicate that platelet derived growth factor (PDGF) plays a pathogenetic role. The aims of the present study were to measure the plasma levels of PDGF across the coronary circulation during PTCA and relate them to the development of restenosis. DESIGN AND RESULTS: Blood samples from the aortic root and coronary sinus were drawn simultaneously before, and after completed PTCA in 26 patients. Plasma levels of PDGF and beta-thromboglobulin (BTG), as well as platelet counts were measured. Restenosis was evaluated by quantitative coronary angiography after 6 months. Significant increases both in PDGF and BTG were encountered in the aortic root after PTCA in patients who developed restenosis as compared to patients without restenosis. Patients who developed restenosis also had significantly higher platelet counts compared to those without. CONCLUSION: Increases in plasma PDGF and BTG in the aortic root after PTCA seem to be markers for restenosis 6 months after PTCA. This finding may strengthen the hypothesis that platelets contribute to the process of restenosis.     

Variation in reporting of pain and other subjective health complaints in a working population and limitations of single sample measurements

Measuring health complaints by administrating a single report is common. Our aim was to assess variation in pain and other subjective complaints over an extended period, whether a single-sample produces representative data, and determine associations between complaints. Health-complaint reports were collected from postal workers at monthly intervals over a period of 32-34 consecutive months (1997-2000). We computed six compound complaint-severity indices of 30 complaint-severity scores (intensity score x duration score, scale 0-9). In 67% of the scores, the complaints exhibited larger deviation from a reference (12 consecutive reports in the last 24 months of the study period) when using one report from the respective reference period compared with the mean of two consecutive reports. Four consecutive samples were needed to obtain agreement for 95% of the data when the criterion of accepted deviation from the reference was set to +/-1.0. Neither inspection of graphs nor statistical tests revealed any seasonal pattern or trend on either a group or individual level. The musculoskeletal and psychological complaint-severity indices correlated strongly (rs > 0.66). Correlations between the different somatic indices were generally weak or moderate (rs < 0.55). The initial report produced higher complaint ratings than subsequent reports did. Due to large intra-individual complaint variability and higher complaint-severity level exhibited on the initial report compared to those that followed, measuring subjective health with a single-sample approach does not produce data representativeness for average complaints over a period. More than two samples should be collected when the purpose is to reveal changes in health.     

Bad news from the brain: descending 5-HT pathways that control spinal pain processing

The identification of opioid systems led to much of the early work on pain pharmacology being based on understanding inhibitory mechanisms of analgesia. However, hyperalgesia and allodynia are common clinical symptoms and therefore hyperexcitability must be a major component of pain. Thus, the emphasis of current research into pain has shifted to understanding excitatory pathways that underlie neuronal sensitization and potentiation. Although much evidence supports the presence of descending inhibitory mechanisms of pain, reports of facilitatory pathways from the brainstem have been scarce. In this article, we review evidence for facilitatory 5-HT pathways that link spinal cord and brainstem areas involved in mood and emotions. Because pain encompasses affective aspects, we suggest that these 5-HT pathways and other circuits are important in determining the levels of pain, the outcome of drug treatments and provide a mechanism whereby emotions can alter pain perception.     

Valproate: past,present, and future

Preclinical studies have been carried out during the past four decades to investigate the different mechanisms of action of valproate (VPA). The mechanisms of VPA which seem to be of clinical importance include increased GABAergic activity, reduction in excitatory neurotransmission, and modification of monoamines. These mechanisms are discussed in relation to the various clinical uses of the drug. VPA is widely used as an antiepileptic drug with a broad spectrum of activity. In patients, VPA possesses efficacy in the treatment of various epileptic seizures such as absence, myoclonic, and generalized tonic-clonic seizures. It is also effective in the treatment of partial seizures with or without secondary generalization and acutely in status epilepticus. The pharmacokinetic aspects of VPA and the frequent drug interactions between VPA and other drugs are discussed. The available methods for the determination of VPA in body fluids are briefly evaluated. At present, investigations and clinical trials are carried out and evaluated to explore the new indications for VPA in other conditions such as in psychiatric disorders, migraine and neuropathic pain. Furthermore, the toxicity of VPA, both regarding commonly occurring side effects and potential idiosyncratic reactions are described. Derivatives of VPA with improved efficacy and tolerability are in development.     

The prognostic impact of cyclin dependent kinase inhibitors p21WAF1, p27Kip1, and p16INK4/MTS1 in adenocarcinomas of the uterine cervix: an immunohistochemical evaluation of expression patterns in population-based material from 142 patients with international federation of gynecology and obstetrics stage I and II adenocarcinoma

BACKGROUND: The authors assessed the prognostic significance of abnormal cyclin dependent kinase inhibitor (CDKI) expression in adenocarcinomas of the uterine cervix. METHODS: Population-based, archival material from patients with International Federation of Gynecology and Obstetrics (FIGO) Stage I and II cervical adenocarcionmas from 2 5-year periods (1976-1980, n = 82 patients; 1986-1990, n = 142 patients) was examined for expression of p21(WAF1), p27(Kip1), and p16(INK4/MTS1) using immunohistochemical techniques. RESULTS: Rates of tumors with low levels of nuclear expression of p27 and p16 were lower during the period 1976-1980 (P < 0.01), suggesting bias due to unbuffered formalin. Analyses that were restricted to patients from 1986-1990 showed positive associations between all three CDKIs (P < 0.05). Low p16 expression was associated with higher FIGO stage (P = 0.01), age older than 55 years (P = 0.01), and deep invasion (P = 0.003). No significant associations with stage, age, or histopathologic parameters were found for p21 or p27. Significant associations with tumor differentiation were not seen for any CDKI. Kaplan-Meier plots showed diverging survival curves for p21 and p27 expression, but the differences were not significant. In multivariate analysis, low p27 expression and high p16 expression were strong predictors of a poor prognosis (p27: < 40% nuclear staining; P = 0.001; hazard ratio, 3.18; p16: < 40% nuclear staining; P < 0.001; hazard ratio, 0.16). Low p27 expression was of prognostic significance only if it was analyzed together with p16 expression. Further evaluation indicated that patients with different phenotypic p27/p16 combinations may have different outcomes. CONCLUSIONS: Aberrant expression patterns of CDKIs were predictors of prognosis for patients with FIGO Stage I or II cervical adenocarcinoma. Analysis of CDKI expression in this patient group may prove clinically useful.