Anti-inflammatory activity of sertaconazole nitrate is mediated via activation of a p38-COX-2-PGE2 pathway

Sertaconazole nitrate is an antifungal agent that exhibits anti-inflammatory activity; however, the mechanism for this action was unknown. We investigated the cellular mechanisms by which sertaconazole exerts its anti-inflammatory activity in keratinocytes and human peripheral blood mononuclear cells (PBMCs). Paradoxically, sertaconazole was found to activate the proinflammatory p38 mitogen-activated protein kinase. Treatment with sertaconazole also resulted in the induction of cyclooxygenase-2 (COX-2) and the subsequent release of prostaglandin E2 (PGE2). Knocking down p38 in keratinocytes using small interfering RNA resulted in an inhibition of sertaconazole-induced PGE2 release confirming that activation of p38 was required for PGE2 production. Additionally, in stimulated keratinocytes and human PBMCs, sertaconazole was found to suppress the release of cytokines. Treatment with anti-PGE2 antiserum or the COX-2 inhibitor NS398 reversed the inhibitory effects of sertaconazole on the release of proinflammatory cytokines, linking endogenous PGE2 with the anti-inflammatory effects. Finally, in an in vivo mouse model of tetradecanoyl phorbol acetate (TPA)-induced dermatitis, the sertaconazole-mediated inhibition of TPA-induced ear edema was reversed by NS398. Biochemical analysis of tissue biopsies revealed increase in PGE2 levels in sertaconazole-treated mice. Thus, activation of the p38-COX-2-PGE2 pathway by agents such as sertaconazole provides anti-inflammatory therapeutic benefits.     

Reproductive health counseling delivered to women living with HIV in the United States

Advances in antiretroviral therapy (ART) and reproductive technologies have made transmission of HIV to partners and infants almost completely preventable. Comprehensive reproductive health counseling (CRHC) is an important component of care for women living with HIV, but few women report discussing reproductive health with an HIV care provider. We surveyed a probability sample of U.S. HIV care providers during 2013–2014. Of 2023 eligible providers, 1234 responded (64% adjusted provider response rate). We estimated the percentage delivering CRHC to their female patients. CRHC was defined as delivering each of five components of reproductive health care to most or all female patients. We assessed associations between provider characteristics and delivering CRHC using chi-squared tests and multivariable logistic regression. Of all providers, 49% (95% confidence interval [CI], 42–55) reported delivering all components of CRHC: 71% assessed reproductive intentions of reproductive-aged women, 78% explained perinatal transmission risk, 87% discussed ART for preventing perinatal transmission, 76% provided contraception as appropriate, and 64% provided referrals for preconception care. Among providers who offered primary care (83% of sample), 52% (CI: 44–60) delivered CRHC compared to 33% (CI: 22–44) of providers who did not offer primary care (P?=?.01). More female providers (46% of sample) compared to male providers delivered CRHC (57% [CI: 48–65] vs. 40% [CI: 31–50], P?相似文献   

Important components of a short-term family group programme. From the Danish National Multicenter Schizophrenia Project

Clinicians from three psychiatric departments have established family groups as a specific intervention for the relatives of patients with first-episode psychosis. The intervention manual is combining the psychoeducational model with psychodynamic understanding and principles. The aim of this study was to identify the special elements of the programme that were the most important to the relatives. A questionnaire was developed for the participants of the groups in order to establish their satisfaction concerning 1) The actual knowledge received; 2) improvement in ability to cooperate with the therapeutic system and other public institutions; 3) the possibility of sharing thoughts, feelings and problems; and 4) dealing with feelings of guilt and shame and the possibility of altering the relationship with the mentally ill relative. Thirty-five relatives of 26 patients filled in the questionnaire consisting of 15 specific items. More than 95% of the relatives appreciated the gained knowledge about schizophrenia as well as the possibility of sharing thoughts and feelings with others. Two specific elements had the highest rating as important factors for the learning condition: 1) to listen to others with similar problems and 2) the group leaders' attitude towards patients and relatives.     

Loss of M5 muscarinic acetylcholine receptors leads to cerebrovascular and neuronal abnormalities and cognitive deficits in mice

The M5 muscarinic acetylcholine receptor (M5R) has been shown to play a crucial role in mediating acetylcholine-dependent dilation of cerebral blood vessels. We show that male M5R-/- mice displayed constitutive constriction of cerebral arteries using magnetic resonance angiography in vivo. Male M5R-/- mice exhibited a significantly reduced cerebral blood flow (CBF) in the cerebral cortex, hippocampus, basal ganglia, and thalamus. Cortical and hippocampal pyramidal neurons from M5R-/- mice showed neuronal atrophy. Hippocampus-dependent spatial and nonspatial memory was also impaired in M5R-/- mice. In M5R-/- mice, CA3 pyramidal cells displayed a significantly attenuated frequency of the spontaneous postsynaptic current and long-term potentiation was significantly impaired at the mossy fiber-CA3 synapse. Our findings suggest that impaired M5R signaling may play a role in the pathophysiology of cerebrovascular deficits. The M5 receptor may represent an attractive novel therapeutic target to ameliorate memory deficits caused by impaired cerebrovascular function.     

Intimate partner violence in Turkey among women with female infertility

In developing countries, failing to conceive is a life crisis with effects on an individual's social life, including stigmatization, loss of social status, marital instability and even conflicts of gender. The aim of this study was to evaluate the relationship between female infertility and intimate partner violence (IPV) in Turkey. This was a cross-sectional study including women with primary infertility who were admitted to University of Health Sciences Ankara Etlik Zubeyde Hanim Health Practice Research Center Hospital between August 2014 and February 2015. IPV was assessed using an Abuse Assessment Screen. Of the 142 participants, 68 (47.9%) confirmed the presence of IPV in their lives. The most common type of violence was psychological, with a prevalence of 76.5% (n = 52), followed by physical, sexual and both physical and sexual abuse, with 17.6% (n = 12), 4.4% (n = 3) and 1.5% (n = 1) prevalence, respectively. Women of low educational and economic level and women living in a compound family were found to be at greater risk for IPV. This high prevalence indicates that Turkey requires new policy for IPV immediately.     

Thyroxine-binding globulin deficiency in early childhood. Postnatal changes in serum concentrations of thyroid hormones and thyroid hormone-binding proteins

Serial determinations of serum thyroxine (T4), triiodothyronine (T3), thyrotropin (TSH), thyroid hormone-binding globulin (TBG), prealbumin (TBPA) and albumin were performed in a euthyroid girl with TBG deficiency and in her mother for a period of 22 months after delivery. At 8 days old the child had a serum TBG concentration around 50% of normal level which remained essentially unchanged during infancy. Total serum T4 and T3 concentrations were low, the free serum T4, free serum T3 and serum TSH concentrations were normal. The mother had received thyroid hormone from the age of 15 years. Her serum TBG level at 6 weeks post partum was similar to that of non-pregnant adults but decreased to about 50% of normal level, indicating a TBG deficiency. She remained euthyroid after withdrawal of T4 therapy. Serum TBPA and albumin concentration were normal in mother and child. An X-linked inheritance of the TBG deficiency was suggested from a study of the family.     

The temporal relationship between schizophrenia and crime

Background Little is known about the temporal relationship between illness onset and the possible beginning of a criminal career among people with schizophrenia, even though criminality, especially violent criminality, has been shown to be more common among people with schizophrenia than among people in general. Aim: The aim of this study was to analyse the temporal relationship between registered crime and contact to the psychiatric hospital system. Method: This is a register-based study merging data on the psychiatric career with criminal records. Results: Among the males with schizophrenia, 37% started a criminal career and 13% had committed first violent crime before first contact with the psychiatric hospital system. Conclusion: The criminality committed before first contact to the psychiatric hospital system is substantial, especially among males with schizophrenia. Accepted: 22 February 2003 Correspondence to Runa Munkner, MD     

Programmed aortic dysfunction and reduced Na+,K+-ATPase activity present in first generation offspring of lard-fed rats does not persist to the second generation

We have previously reported that male and female offspring of Sprague-Dawley rats fed a diet rich (approximately 50% of caloric intake from fat) in animal fat (lard) during pregnancy and suckling (OHF) demonstrate cardiovascular dysfunction, including blunted endothelium-dependent vasodilatation in the aorta as well as reduced renal Na(+),K(+)-ATPase activity. Cardiovascular dysfunction has been reported in other models of developmental programming and some researchers describe transmission from F(1) to F(2) generations. Here we report a study of vascular function, as assessed in isolated rings of aorta mounted in an organ bath, and renal Na(+),K(+)-ATPase activity in 6-month-old male and female F(2) offspring of lard-fed and control-fed (OC) dams (n = 13 per diet group). An increase in brain (OC 0.61 +/- 0.01% versus OHF 0.66 +/- 0.02% of bodyweight) and kidney weights (OC 0.32 +/- 0.01% versus OHF 0.37 +/- 0.01% of bodyweight) was observed in female F(2) offspring of lard-fed dams compared with F(2) controls (P < 0.03). Constrictor responses to phenylephrine in the aorta were not different from F(2) controls (repeated measures ANOVA, P = 0.85). Also, endothelium-dependent dilator function, as assessed by responses to acetylcholine (repeated measures ANOVA, P = 0.96) and passive distensibility in the absence of extracellular calcium (repeated measures ANOVA, P = 0.68), was similar. Additionally, renal Na(+),K(+)-ATPase activity was not statistically different from that observed in control animals (ANOVA, P = 0.89). Although a maternal diet rich in animal fat has deleterious effects on parameters of cardiovascular risk in F(1) animals, it does not appear that disorders previously reported in the F(1) generation are transmitted to the F(2) generation.