Progesterone reduces erectile dysfunction in sleep-deprived spontaneously hypertensive rats

BACKGROUND: Paradoxical sleep deprivation (PSD) associated with cocaine has been shown to enhance genital reflexes (penile erection-PE and ejaculation-EJ) in Wistar rats. Since hypertension predisposes males to erectile dysfunction, the aim of the present study was to investigate the effects of PSD on genital reflexes in the spontaneously hypertensive rat (SHR) compared to the Wistar strain. We also extended our study to examine how PSD affect steroid hormone concentrations involved in genital events in both experimental models. METHODS: The first experiment investigated the effects of PSD on genital reflexes of Wistar and SHR rats challenged by saline and cocaine (n = 10/group). To further examine the impact of the PSD on concentrations of sexual hormones, we performed a hormonal analysis of testosterone and progesterone in the Wistar and in SHR strains. Since after PSD progesterone concentrations decreased in the SHR compared to the Wistar PSD group we extended our study by investigating whether progesterone (25 mg/kg or 50 mg/kg) or testosterone (0.5 mg/kg or 1.0 mg/kg) administration during PSD would have a facilitator effect on the occurrence of genital reflexes in this hypertensive strain. RESULTS: A 4-day period of PSD induced PE in 50% of the Wistar rats against 10% for the SHR. These genital reflexes was potentiated by cocaine in Wistar rats whereas this scenario did not promote significant enhancement in PE and EJ in hypertensive rats, and the percentage of SHR displaying genital reflexes still figured significantly lower than that of the Wistar strain. As for hormone concentrations, both sleep-deprived Wistar and SHR showed lower testosterone concentrations than their respective controls. Sleep deprivation promoted an increase in concentrations of progesterone in Wistar rats, whereas no significant alterations were found after PSD in the SHR strain, which did not present enhancement in erectile responses. In order to explore the role of progesterone in the occurrence of genital reflexes, SHR were treated daily during the sleep deprivation period with progesterone; after the administration of this hormone and challenge with cocaine, we observed a significant increase in erectile events compared with the vehicle PSD SHR+cocaine group. CONCLUSION: Our data showed that the low frequency of genital reflexes found in SHR sleep deprived rats may be attributed to the lower concentrations of progesterone in these rats, based on the observation that progesterone replacement increased genital reflexes in this strain

Surface Localization of Glucosylceramide during Cryptococcus neoformans Infection Allows Targeting as a Potential Antifungal

Cryptococcus neoformans (Cn) is a significant human pathogen that, despite current treatments, continues to have a high morbidity rate especially in sub-Saharan Africa. The need for more tolerable and specific therapies has been clearly shown. In the search for novel drug targets, the gene for glucosylceramide synthase (GCS1) was deleted in Cn, resulting in a strain (Δgcs1) that does not produce glucosylceramide (GlcCer) and is avirulent in mouse models of infection. To understand the biology behind the connection between virulence and GlcCer, the production and localization of GlcCer must be characterized in conditions that are prohibitive to the growth of Δgcs1 (neutral pH and high CO2). These prohibitive conditions are physiologically similar to those found in the extracellular spaces of the lung during infection. Here, using immunofluorescence, we have shown that GlcCer localization to the cell surface is significantly increased during growth in these conditions and during infection. We further seek to exploit this localization by treatment with Cerezyme (Cz), a recombinant enzyme that metabolizes GlcCer, as a potential treatment for Cn. Cz treatment was found to reduce the amount of GlcCer in vitro, in cultures, and in Cn cells inhabiting the mouse lung. Treatment with Cz induced a membrane integrity defect in wild type Cn cells similar to Δgcs1. Cz treatment also reduced the in vitro growth of Cn in a dose and condition dependent manner. Finally, Cz treatment was shown to have a protective effect on survival in mice infected with Cn. Taken together, these studies have established the legitimacy of targeting the GlcCer and other related sphingolipid systems in the development of novel therapeutics

Pyoderma gangrenosum after totally implanted central venous access device insertion

<p>Abstract</p> <p>Background</p> <p>Pyoderma gangrenosum is an aseptic skin disease. The ulcerative form of pyoderma gangrenosum is characterized by a rapidly progressing painful irregular and undermined bordered necrotic ulcer. The aetiology of pyoderma gangrenosum remains unclear. In about 70% of cases, it is associated with a systemic disorder, most often inflammatory bowel disease, haematological disease or arthritis. In 25–50% of cases, a triggering factor such as recent surgery or trauma is identified. Treatment consists of local and systemic approaches. Systemic steroids are generally used first. If the lesions are refractory, steroids are combined with other immunosuppressive therapy or to antimicrobial agents.</p> <p>Case presentation</p> <p>A 90 years old patient with myelodysplastic syndrome, seeking regular transfusions required totally implanted central venous access device (Port-a-Cath^®) insertion. Fever and inflammatory skin reaction at the site of insertion developed on the seventh post-operative day, requiring the device's explanation. A rapid progression of the skin lesions evolved into a circular skin necrosis. Intravenous steroid treatment stopped the necrosis' progression.</p> <p>Conclusion</p> <p>Early diagnosis remains the most important step to the successful treatment of pyoderma gangrenosum.</p

Penyuluhan dan Pelayanan Kesehatan Sebagai Upaya Memperbaiki Manajemen Hipertensi Pada Lansia Di Kelurahan Jembatan Lima Kecamatan Tambora Jakarta

The incidence of hypertension increases with age. Alterations in function and structure in peripheral vascular system are thought to be the cause of high prevalence of hypertension in the elderly. Holistic, patient-centered management of hypertension is needed to prevent deaths from heart failure. This community service aimed to find out the level of knowledge about hypertension in residents of Jembatan Lima Sub-district, Tambora District, West Jakarta. Using a questionnaire, the level of knowledge was studied in 48 participants cross-sectionally. Blood pressure measurements were also carried out to describe the incidence of hypertension in that area. There was a low level of knowledge about hypertension among participants and this had an impact on increasing the risk of hypertension. Fifty-two percent of participants had normal blood pressure, whereas 48% participants were diagnosed as hypertension. Based on demographic data of participants obtained during the event, age, sex, education level and type of work were significantly increasing the risk of hypertension. Results from this community service conclude that the lack of knowledge of hypertension especially in the elderly can increase the risk of hypertension. In order to improve the quality of managing hypertension in the elderly in Jembatan Lima Village, Tambora District, West Jakarta, it is recommended that counseling and discussion groups to be held annually, especially among the elderly.Angka kejadian hipertensi meningkat seiring dengan meningkatnya usia. Perubahan fungsi dan struktur pada sistem vaskuler perifer diperkirakan menjadi penyebab tingginya prevalensi hipertensi pada lansia. Manajemen hipertensi secara holistik yang terpusat pada pasien diperlukan untuk mencegah terjadinya kematian akibat gagal jantung. Pengabdian Kepada Masyarakat &nbsp;ini dilakukan untuk mengetahui gambaran tingkat pengetahuan hipertensi pada lansia di Kecamatan Tambora Jakarta Barat. Dengan menggunakan kuesioner, tingkat pengetahuan tentang hipertensi diukur pada 48 peserta di tempat tersebut. Pengukuran tekanan darah juga dilakukan untuk mendeskripsikan tingkat kejadian hipertensi di tempat tersebut. Tingkat pengetahuan tentang hipertensi para peserta kegiatan pengabdian kepada masyarakat kurang baik dan berdampak pada meningkatkan risiko hipertensi. 52% peserta memiliki tekanan darah normal sedangkan 48% peserta terdiagnosis hipertensi. Faktor risiko berdasarkan data demografi peserta juga didapatkan dengan hasil usia, jenis kelamin, tingkat pendidikan serta jenis pekerjaan meningkatkan risiko hipertensi secara bermakna. Dari hasil PKM ini dapat disimpulkan bahwa kurangnya tingkat pengetahuan hipertensi khususnya pada lansia dapat meningkatkan risiko terjadinya hipertensi. Agar dapat meningkatkan kualitas penanganan hipertensi pada lansia di Kelurahan Jembatan Lima Kecamatan Tambora Jakarta barat, maka disarankan agar diadakan penyuluhan dan grup diskusi antar lansia

Primary tubercular liver abscess in an immunocompetent adult: a case report

<p>Abstract</p> <p>Introduction</p> <p>Isolated primary tubercular abscess is one of the rare forms of extrapulmonary tuberculosis. A greater awareness of this rare clinical entity may help in commencing specific evidence-based therapy quickly and preventing undue morbidity and mortality.</p> <p>Case presentation</p> <p>A 30-year-old man, of Asian origin, developed a hepatic tubercular abscess which was not associated with any pulmonary or gastrointestinal tract foci of tuberculosis. An ultrasonogram of the abdomen showed an abscess in the right lobe of his liver which was initially diagnosed as an amoebic liver abscess. Subsequently, the pus from the lesion yielded <it>Mycobacterium tuberculosis </it>using the BACTEC TB 460 instrument and <it>Mycobacterium tuberculosis </it>deoxyribonucleic acid by polymerase chain reaction. The patient was started on systemic antitubercular therapy to which he responded favorably.</p> <p>Conclusion</p> <p>This report emphasizes the fact that, although a tuberculous liver abscess is a very rare entity, it should be included in the differential diagnosis of unknown hepatic mass lesions.</p

The Effect of Epstein-Barr Virus Latent Membrane Protein 2 Expression on the Kinetics of Early B Cell Infection

Infection of human B cells with wild-type Epstein-Barr virus (EBV) in vitro leads to activation and proliferation that result in efficient production of lymphoblastoid cell lines (LCLs). Latent Membrane Protein 2 (LMP2) is expressed early after infection and previous research has suggested a possible role in this process. Therefore, we generated recombinant EBV with knockouts of either or both protein isoforms, LMP2A and LMP2B (Δ2A, Δ2B, Δ2A/Δ2B) to study the effect of LMP2 in early B cell infection. Infection of B cells with Δ2A and Δ2A/Δ2B viruses led to a marked decrease in activation and proliferation relative to wild-type (wt) viruses, and resulted in higher percentages of apoptotic B cells. Δ2B virus infection showed activation levels comparable to wt, but fewer numbers of proliferating B cells. Early B cell infection with wt, Δ2A and Δ2B viruses did not result in changes in latent gene expression, with the exception of elevated LMP2B transcript in Δ2A virus infection. Infection with Δ2A and Δ2B viruses did not affect viral latency, determined by changes in LMP1/Zebra expression following BCR stimulation. However, BCR stimulation of Δ2A/Δ2B cells resulted in decreased LMP1 expression, which suggests loss of stability in viral latency. Long-term outgrowth assays revealed that LMP2A, but not LMP2B, is critical for efficient long-term growth of B cells in vitro. The lowest levels of activation, proliferation, and LCL formation were observed when both isoforms were deleted. These results suggest that LMP2A appears to be critical for efficient activation, proliferation and survival of EBV-infected B cells at early times after infection, which impacts the efficient long-term growth of B cells in culture. In contrast, LMP2B did not appear to play a significant role in these processes, and long-term growth of infected B cells was not affected by the absence of this protein. © 2013 Wasil et al

Dose-dense adjuvant chemotherapy for primary breast cancer

Adjuvant chemotherapy has been proven to reduce significantly the risk for relapse and death in women with operable breast cancer. Nevertheless, the prognosis for patients presenting with extensive axillary lymph node involvement remains suboptimal. In an attempt to improve on the efficacy of existing chemotherapy, a phase III intergroup trial led by the Cancer and Leukemia Group B (CALGB 97-41) was designed, which tested a mathematical model of tumor growth based on the Norton–Simon hypothesis. This hypothesis, developed about 3 decades ago, and the kinetic model derived from it, created the basis of the concepts of dose density and sequential therapy, both of which were tested in CALGB 97-41. This large prospective randomized trial demonstrated that shortening the time interval between each chemotherapy cycle while maintaining the same dose size resulted in significant improvements in disease-free and overall survival in patients with node-positive breast carcinoma. This finding is highly relevant and has immediate implications for clinical practice

Angiostatin anti-angiogenesis requires IL-12: The innate immune system as a key target

© 2009 Albini et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens