33 research outputs found
Dynamics of adaptive response and immune reactivity under the influence of adaptogenic drugs in pulmonary tuberculosis
Chiril Draganiuc Institute of Phthysiopneumology,
Department of Pneumophthysiology, Nicolae Testemitsanu State University of Medicine and Pharmacy, Chisinau, the Republic of MoldovaBackground: Tuberculosis is a multifactorial disease, with the evolution and response to treatment being determined by the interaction between the genotype of M. tuberculosis and the human genotype. Immunological adaptogenic treatment is an important pathogenetical treatment of tuberculosis. BioR medicine obtained from the biomass of Spirulina platensis exhibits an antioxidant activity and immunomodulator activity. Extract of Eleuterococc increases the bodyâs resistance, diminishing the level of the body stress syndrome. The aim of the research was the comparative analysis of adaptive reactivity and immune resistance in the patients with pulmonary tuberculosis treated with immunomodulator drug BioR versus extract of Eleuterococ. Material and methods: adaptive reactivity and immune resistance indices were analyzed in a total number of 113 patients hospitalized in clinical subdivisions of Chiril Draganiuc Institute of Pneumophthysiology. Results: Both drugs showed a high adaptogenic capacity, a high efficiency on the level of immune reactivity, although it was appreciated that the immune modulator drug BioR is more efficient than Eleuterococ extract associated medicine to antituberculois treatment of patients with pulmonary tuberculosis. Conclusions: The combination of adaptogenic drugs: extract of Eleuterococ and BioR with anti-TB treatment enhances its efficacy, demonstrated by normalizing of the adaptogenic reactions, also enhancing the immune and preimmune resistance indices. Both drugs can be recommended for inclusion as immune modulators in the standard anti-TB treatment with the aim to ensure high therapeutical effectiveness
Microcapteurs électrochimiques pour des mesures durables en Environnement-Santé et Agroalimentaire
National audienc
Caspase-3 dependent nitrergic neuronal apoptosis following cavernous nerve injury is mediated via RhoA and ROCK activation in major pelvic ganglion
Axonal injury due to prostatectomy leads to Wallerian degeneration of the cavernous nerve (CN) and erectile dysfunction (ED). Return of potency is dependent on axonal regeneration and reinnervation of the penis. Following CN injury (CNI), RhoA and Rho-associated protein kinase (ROCK) increase
in penile endothelial and smooth muscle cells. Previous studies indicate that nerve regeneration is hampered by activation of RhoA/ROCK pathway. We evaluated the role of RhoA/ROCK pathway in CN regulation following CNI using a validated rat model. CNI upregulated gene and protein expression of RhoA/ROCK and caspase-3 mediated apoptosis in the major pelvic ganglion (MPG). ROCK inhibitor (ROCK-I) prevented upregulation of RhoA/ROCK pathway as well as activation of caspase-3 in the MPG. Following CNI, there was decrease in the dimer to monomer ratio of neuronal nitric oxide synthase (nNOS) protein and lowered NOS activity in the MPG, which were prevented by ROCK-I. CNI lowered intracavernous pressure and impaired non-adrenergic non-cholinergic-mediated relaxation in the penis, consistent with ED. ROCK-I maintained the intracavernous pressure and non-adrenergic non-cholinergic-mediated relaxation in the penis following CNI. These results suggest that activation of RhoA/ROCK pathway mediates caspase-3 dependent apoptosis of nitrergic neurons in the MPG following CNI and that ROCK-I can prevent post-prostatectomy ED
A High Incidence of Meiotic Silencing of Unsynapsed Chromatin Is Not Associated with Substantial Pachytene Loss in Heterozygous Male Mice Carrying Multiple Simple Robertsonian Translocations
Meiosis is a complex type of cell division that involves homologous chromosome pairing, synapsis, recombination, and segregation. When any of these processes is altered, cellular checkpoints arrest meiosis progression and induce cell elimination. Meiotic impairment is particularly frequent in organisms bearing chromosomal translocations. When chromosomal translocations appear in heterozygosis, the chromosomes involved may not correctly complete synapsis, recombination, and/or segregation, thus promoting the activation of checkpoints that lead to the death of the meiocytes. In mammals and other organisms, the unsynapsed chromosomal regions are subject to a process called meiotic silencing of unsynapsed chromatin (MSUC). Different degrees of asynapsis could contribute to disturb the normal loading of MSUC proteins, interfering with autosome and sex chromosome gene expression and triggering a massive pachytene cell death. We report that in mice that are heterozygous for eight multiple simple Robertsonian translocations, most pachytene spermatocytes bear trivalents with unsynapsed regions that incorporate, in a stage-dependent manner, proteins involved in MSUC (e.g., ÎłH2AX, ATR, ubiquitinated-H2A, SUMO-1, and XMR). These spermatocytes have a correct MSUC response and are not eliminated during pachytene and most of them proceed into diplotene. However, we found a high incidence of apoptotic spermatocytes at the metaphase stage. These results suggest that in Robertsonian heterozygous mice synapsis defects on most pachytene cells do not trigger a prophase-I checkpoint. Instead, meiotic impairment seems to mainly rely on the action of a checkpoint acting at the metaphase stage. We propose that a low stringency of the pachytene checkpoint could help to increase the chances that spermatocytes with synaptic defects will complete meiotic divisions and differentiate into viable gametes. This scenario, despite a reduction of fertility, allows the spreading of Robertsonian translocations, explaining the multitude of natural Robertsonian populations described in the mouse
Results of a phase 1, randomized, placebocontrolled first-in-human trial of griffithsin formulated in a carrageenan vaginal gel
HIV pre-exposure prophylaxis (PrEP) is dominated by clinical therapeutic antiretroviral (ARV) drugs. Griffithsin (GRFT) is a non-ARV lectin with potent anti-HIV activity. GRFTâs preclinical safety, lack of systemic absorption after vaginal administration in animal studies, and lack of cross-resistance with existing ARV drugs prompted its development for topical HIV PrEP. We investigated safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of PC-6500 (0.1% GRFT in a carrageenan (CG) gel) in healthy women after vaginal administration. This randomized, placebo-controlled, parallel group, double-blind first-in-human phase 1 study enrolled healthy, HIV-negative, non-pregnant women aged 24â45 years. In the open label period, all participants (n = 7) received single dose of PC- 6500. In the randomized period, participants (n = 13) were instructed to self-administer 14 doses of PC-6500 or its matching CG placebo (PC-535) once daily for 14 days. The primary outcomes were safety and PK after single dose, and then after 14 days of dosing. Exploratory outcomes were GRFT concentrations in cervicovaginal fluids, PD, inflammatory mediators and gene expression in ectocervical biopsies. This trial is registered with ClinicalTrials. gov, number NCT02875119. No significant adverse events were recorded in clinical or laboratory results or histopathological evaluations in cervicovaginal mucosa, and no anti-drug (GRFT) antibodies were detected in serum. No cervicovaginal proinflammatory responses and no changes in the ectocervical transcriptome were evident. Decreased levels of proinflammatory chemokines (CXCL8, CCL5 and CCL20) were observed. GRFT was not detected in plasma. GRFT and GRFT/CG in cervicovaginal lavage samples inhibited HIV and HPV, respectively, in vitro in a dose-dependent fashion. These data suggest GRFT formulated in a CG gel is a safe and promising on-demand multipurpose prevention technology product that warrants further investigation
SLXL1, a novel acrosomal protein, interacts with DKKL1 and is involved in fertilization in mice
BACKGROUND: Spermatogenesis is a complex cellular developmental process which involves diverse families of genes. The Xlr (X-linked, lymphocyte regulated) family includes multiple members, only a few of which have reported functions in meiosis, post-meiotic maturation, and fertilization of germ cells. Slx-like1 (Slxl1) is a member of the Xlr family, whose expression and function in spermatogenesis need to be elucidated. METHODOLOGY/PRINCIPAL FINDINGS: The mRNA and protein expression and localization of Slxl1 were investigated by RT-PCR, Western blotting and immunohistochemistry in different tissues and at different stages of spermatogenesis. The interacting partner of SLXL1 was examined by co-immunoprecipitation and co-localization. Assessment of the role of SLXL1 in capacitation, acrosome reaction, zona pellucida binding/penetration, and fertilization was carried out in vitro using blocking antisera. The results showed that Slxl1 mRNA and protein were specifically expressed in the testis. SLXL1 was exclusively located in the acrosome of post-meiotic germ cells and interacts with DKKL1 (Dickkopf-like1), which is an acrosome-associated protein and plays an important role in fertilization. The rates of zona pellucida binding/penetration and fertilization were significantly reduced by the anti-SLXL1 polyclonal antiserum. CONCLUSIONS/SIGNIFICANCE: SLXL1 is the first identified member of the XLR family that is associated with acrosome and is involved in zona pellucid binding/penetration and subsequent fertilization. These results, together with previous studies, suggest that Xlr family members participate in diverse processes from meiosis to fertilization during spermatogenesis
Secondary surgical decompression of the inferior alveolar nerve after overfilling of endodontic sealer into the mandibular canal: Case report and literature review
International audienceThe authors report the case of a 43-year-old woman who underwent endodontic treatment of the right second mandibular molar with substantial extrusion of endodontic material into the mandibular canal. The patient presented at the Department of Oral and Maxillofacial Surgery with a persistent total anaesthesia of the lower lip and chin after two months. 2D panoramic view and 3D CT-scan examination highlighted the overfilling into the mandibular canal with a more than 50% stenosis of the canal and a consequently significant compression of the dental pedicle. A surgical decompression of the inferior alveolar nerve was performed through an inferior vestibular approach, using PiezoSurgeryÂź. The tooth was conserved. After a period of 8days, paraesthesia of the lower lip and chin appeared. Thermoalgic sensitivity was recovered at 1month. At 3months postoperatively, the patient had recovered protopathic and epicritic sensitivity. Dental prosthetic rehabilitation was finally achieved one year postoperatively. The authors discuss the physiopathology of nervous injuries during dental procedures, and further strategies in the case of persistent neurologic disorders
Reversal of diabetic vasculopathy in a rat model of type 1 diabetes by opiorphin-related peptides
Microcapteurs électrochimiques pour des mesures durables en Environnement, Santé et Agroalimentaire
National audienc
Physician experts in diabetes are natural team leaders for managing diabetic patients with foot complications. A position statement from the Italian diabetic foot study group
Diabetic foot syndrome (DFS) is a complex disease. The best outcomes are reported with the multi-disciplinary team (MDT) approach, where each member works collaboratively according to his/her expertise. However, which health provider should act as the team leader (TL) has not been determined. The TL should be familiar with the management of diabetes, related complications and comorbidities. He/she should be able to diagnose and manage foot infections, including prompt surgical treatment of local lesions, such as abscesses or phlegmons, in an emergent way in the first meeting with the patient. According to the Organization for Economic Co-operation and Development (OECD) reports, Italy is one of countries with a low amputation rate in diabetic patients. Many factors might have contributed to this result, including 1)the special attention directed to diabetes by the public health system, which has defined diabetes as a "protected disease", and accordingly, offers diabetic patients, at no charge, the best specialist care, including specific devices, and 2)the presence of a network of diabetic foot (DF) clinics managed by diabetologists with medical and surgical expertise. The health care providers all share a "patient centred model" of care, for which they use their internal medicine background and skills in podiatric surgery to manage acute or chronic needs in a timely manner. Therefore, according to Italian experiences, which are fully reported in this document, we believe that only a skilled diabetologist/endocrinologist should act as a TL. Courses and university master's degree programmes focused on DF should guarantee specific training for physicians to become a TL