Liver growth factor induces testicular regeneration in EDS-treated rats and increases protein levels of class B scavenger receptors.

The aim of the present work was to determine the effects of liver growth factor (LGF) on the regeneration process of rat testes after chemical castration induced by ethane dimethanesulfonate (EDS) by analyzing some of the most relevant proteins involved in cholesterol metabolism, such as hormone sensitive lipase (HSL), 3ß-hydroxysteroid dehydrogenase (3ß-HSD), scavenger receptor SR-BI, and other components of the SR family that could contribute to the recovery of steroidogenesis and spermatogenesis in the testis. Sixty male rats were randomized to nontreated (controls) and LGF-treated, EDS-treated, and EDS + LGF-treated groups. Testes were obtained on days 10 (T1), 21 (T2), and 35 (T3) after EDS treatment, embedded in paraffin, and analyzed by immunohistochemistry and Western blot. LGF improved the recovery of the seminiferous epithelia, the appearance of the mature pattern of Leydig cell interstitial distribution, and the expression of mature SR-BI. Moreover, LGF treatment resulted in partial recovery of HSL expression in Leydig cells and spermatogonia. No changes in serum testosterone were observed in control or LGF-treated rats, but in EDS-castrated animals LGF treatment induced a progressive increase in serum testosterone levels and 3ß-HSD expression. Based on the pivotal role of SR-BI in the uptake of cholesteryl esters from HDL, it is suggested that the observed effects of LGF would facilitate the provision of cholesterol for sperm cell growth and Leydig cell recovery.

Circulating free testosterone in obese men after bariatric surgery increases in parallel with insulin sensitivity.

BACKGROUND AND AIM: Male hypogonadism has been linked to obesity and diabetes. We aimed to study the association of changes in insulin sensitivity and testosterone levels in severe obese patients submitted to bariatric surgery. SUBJECTS AND METHODS: Prospective intervention study with twenty consecutive patients who underwent bariatric surgery studied before and after significant weight loss. Serum testosterone, SHBG, fasting glucose, and insulin were measured among others. Free testosterone was calculated with the Vermeulen formula and insulin sensitivity with the homeostatic model assessment (HOMA). RESULTS: At baseline, thirteen patients had low total testosterone levels, whereas eight of these patients also had free testosterone levels below the reference range obtained from the control group. After bariatric surgery total testosterone, SHBG, and free testosterone significantly increased and achieved normal values in all evaluated patients. Insulin sensitivity improved in all of them. Multivariate linear regression showed that changes in fasting glucose (ß=-1.868, p=0.001), insulin (ß=-3.782, p=0.001), weight (ß=-0.622, p=0.002), and SHBG (ß=-0.635, p=0.022) were associated with changes in free testosterone (adjusted R2=0.936, F=26.613, p=0.001). When insulin resistance calculated by HOMA was in the model instead of insulin and glucose, it also was associated (ß=-3.488, p=0.008) with free testosterone (adjusted R2=0.821, F=11.111, p=0.005). CONCLUSIONS: Circulating tes tos terone in obese men increases after bariatric surgery in parallel with an improvement in insulin sensitivity.

[Virtual consultations in Traumatology and Orthopaedic Surgery]. / Consultas virtuales en Traumatología y Cirugía Ortopédica.

OBJECTIVE: The objective of this study is to analyse the current system of virtual consultations between the levels of Primary and Specialised Care in the field of Traumatology and Orthopaedic Surgery (TOS) in our healthcare area. MATERIAL AND METHOD: A retrospective observational study was carried out on 90 consecutive patients who had a non-face-to-face consultation between 3 January 2017 and 10 February 2017 and subsequently a face-to-face consultation. All the patients belonged to the same healthcare area attached to the Nuestra Señora de Candelaria University Hospital. The data on the diagnostic orientation, medical history provided and complementary tests were evaluated by 2 observers, one with training in Family and Community Medicine and the other with specialised training in TOS, and compared with those obtained in the final face-to-face assessment. RESULTS: The results showed a low inter-judge agreement regarding the diagnostic orientation, anamnesis, exploration and complementary tests provided in the virtual consultation request. It was considered that only 59% for one observer (Family and Community Medicine) and 47.7% for the other (specialised care) had sufficient information for decision-making. Furthermore, 35.2% required more than one face-to-face assessment consultation until diagnosis and in 45.5% it was necessary to request new complementary tests. In 30.7%, there was no concordance in the suggested and final diagnosis. In 51.9%, no therapeutic action other than that carried out by Primary Care was carried out and 34.1% of the patients were referred to the Rehabilitation department. CONCLUSIONS: The current model of virtual consultations in TOS does not seem adequate to respond to this new healthcare model. The number of unnecessary referrals is very high despite the previous virtual assessment by a specialist in TOS. The Family and Community Medicine specialist should have more diagnostic resources and coordination between Primary and Specialised Care is necessary to determine, in the area of TOS, the type of consultations and conditions for which this system should be implemented to obtain adequate coordination and improve communication between both levels of care.

Clinical characterisation of pneumonia caused by atypical pathogens combining classic and novel predictors.

The aim of this study was to characterise community-acquired pneumonia (CAP) caused by atypical pathogens by combining distinctive clinical and epidemiological features and novel biological markers. A population-based prospective study of consecutive patients with CAP included investigation of biomarkers of bacterial infection, e.g., procalcitonin, C-reactive protein and lipopolysaccharide-binding protein (LBP) levels. Clinical, radiological and laboratory data for patients with CAP caused by atypical pathogens were compared by univariate and multivariate analysis with data for patients with typical pathogens and patients from whom no organisms were identified. Two predictive scoring models were developed with the most discriminatory variables from multivariate analysis. Of 493 patients, 94 had CAP caused by atypical pathogens. According to multivariate analysis, patients with atypical pneumonia were more likely to have normal white blood cell counts, have repetitive air-conditioning exposure, be aged <65 years, have elevated aspartate aminotransferase levels, have been exposed to birds, and have lower serum levels of LBP. Two different scoring systems were developed that predicted atypical pathogens with sensitivities of 35.2% and 48.8%, and specificities of 93% and 91%, respectively. The combination of selected patient characteristics and laboratory data identified up to half of the cases of atypical pneumonia with high specificity, which should help clinicians to optimise initial empirical therapy for CAP.

[Salivary cortisol determination in the diagnosis of pediatric Cushing's disease]. / Determinación de cortisol salival en el diagnóstico de la enfermedad de Cushing pediátrico.

Endogenous Cushing's syndrome in children is a very rare entity. Diagnosis is complex due to the wide variety of tests available. Recently, the utility of salivary cortisol has been proposed for the diagnosis of this entity, although greater evidence is required, especially in pediatric patients. We report a 14-year-old girl with Cushing's disease due to a pituitary microadenoma in whom salivary cortisol determination was very useful for the diagnosis.

Insulin-induced up-regulation of lipoprotein lipase messenger ribonucleic acid and activity in mammary gland.

The effects of insulin on lipoprotein lipase (LPL) messenger RNA (mRNA) were studied in mammary glands from virgin and late-pregnant rats. Virgin and pregnant rats (at 17 days of gestation) were subjected to a continuous infusion (35 ml/day) with 50% glucose for 72 h to produce a prolonged hyperinsulinemic-euglycemic condition. Gestation causes a 4-fold increase in LPL mRNA accompanied by a 3- to 4-fold increase in total LPL activity. Experimental hyperinsulinemia, generated by the 50% glucose infusion, had a similar effect in both pregnant and virgin rats, by enhancing (2- to 3-fold) both their LPL activity and LPL mRNA. Thus, total LPL activity and LPL mRNA significantly correlated with plasma insulin (r = 0.789, P < 0.001; and r = 0.772, P < 0.001, respectively). Furthermore, total LPL activity was correlated with LPL mRNA (r = 0.765, P = 0.001). In conclusion, the present study shows that insulin participates in the control of LPL expression in mammary glands, revealing its role as a modulator of the enzyme at a mRNA level.

Localization of the lipid receptors CD36 and CLA-1/SR-BI in the human gastrointestinal tract: towards the identification of receptors mediating the intestinal absorption of dietary lipids.

The scavenger receptors CLA-1/SR-BI and CD36 interact with native and modified lipoproteins and with some anionic phospholipids. In addition, CD36 binds/transports long-chain free fatty acids. Recent biochemical evidences indicates that the rabbit CLA-1/SR-BI receptor can be detected in enterocytes, and previous studies showed the presence of mRNA for both CLA-1/SR-BI and CD36 in some segments of the intestinal tract. These findings prompted us to study their respective localization and distribution from the human stomach to the colorectal segments, using immunohistochemical methods. Their expression in the colorectal carcinoma-derived cell line Caco-2 was analyzed by Northern blotting. In the human intestinal tract, CLA-1/SR-BI was found in the brush-border membrane of enterocytes from the duodenum to the rectum. However, CD36 was found only in the duodenal and jejunal epithelium, whereas enterocytes from other intestinal segments were not stained. In the duodenum and jejunum, CD36 co-localized with CLA-1/SR-BI in the apical membrane of enterocytes. The gastric epithelium was immunonegative for both glycoproteins. We also found that CLA-1/SR-BI mRNA was expressed in Caco-2 cells and that its expression levels increased concomitantly with their differentiation. In contrast, the CD36 transcript was not found in this colon cell line, in agreement with the absence of this protein in colon epithelium. The specific localization of CLA-1/SR-BI and CD36 along the human gastrointestinal tract and their ability to interact with a large variety of lipids strongly support a physiological role for them in absorption of dietary lipids.

Corynebacterium pseudodiphtheriticum: an easily missed respiratory pathogen in HIV-infected patients.

Despite being a well-known respiratory pathogen for immunocompromised patients, Corynebacterium pseudodiphtheriticum has uncommonly been reported to occur in persons with infection attributable to HIV virus. We report three cases of respiratory tract infection attributable to C. pseudodiphtheriticum in HIV-infected patients and review the four previous cases from the medical literature. All of them were male with a median CD4 lymphocyte count of 110 cells/mm3 (range, 18-198/mm3); five of the seven cases occurred in persons for whom AIDS was diagnosed previously. The onset of symptomatology was usually acute and the most common radiographic appearance was alveolar infiltrate (six patients) with cavitation (two patients) and pleural effusion (two patients). In five of the seven cases, C. pseudodiphtheriticum was isolated from bronchoscopic samples and in the remaining two cases was recovered from lung biopsy (one patient) and sputum (one patient). In the three patients reported herein and in one previous case from the medical literature, quantitative culturing of bronchoscopic samples obtained through either bronchoalveolar lavage or protected brush catheter procedures yielded more than 10(3) CFU/mL. All the strains tested were susceptible to penicillin and vancomycin. Resistance to macrolides was common. Recovery was observed in six of the seven patients. C. pseudodiphtheriticum should be regarded as a potential respiratory pathogen in HIV-infected patients. This infection presents late in the course of HIV disease and it seems to respond well to appropriate antibiotic treatment in most of the cases. This easily overlooked pathogen should be added to the list of organisms implicated in respiratory tract infections in this population.

Effects of ethanol intake on lipid metabolism in the lactating rat.

Female rats receiving alcohol (20%) in drinking water during lactation (AL) were compared to pair-fed animals (PF) and normal controls (C) fed ad lib. All animals were killed on the 12th day of lactation. When compared to C rats, food intake decreased in both AL and PF groups, and this effect was followed by a lower body weight and mammary gland (MG), liver, and parametrial adipose tissue weights. Mammary glands triacylglyceride concentration (TG) was much lower in PF than in AL, although in the latter, values did not reach those of C, and had higher liver TG concentration than any of the other groups. Both PF and AL rats had lower plasma TG, glycerol, and free fatty acid concentrations and higher beta-hydroxybutyrate concentration than C rats. When compared to C rats, the rate of lipogenesis in MG was higher in both PF and AL rats, whereas in liver it was higher in PF and lower in AL rats, and in adipose tissue it was higher in PF and unchanged in AL rats. The appearance of 14C lipids 4 h after oral [14]triolein in both MG and liver was lower in AL and PF rats and only lower in adipose tissue of AL rats as compared to the c rats. Lipoprotein lipase and hormone-sensitive lipase activities were lower in MG in both PF and AL rats than in C, whereas in adipose tissue the activity of lipoprotein lipase did not differ between AL and C rats and the activity of HSL was lower in the former. These findings therefore show that in spite of reduced uptake of orally administered triglycerides due to decreased LPL activity, maternal alcohol feeding during lactation in the rat preserves the mammary gland triglyceride content thanks to enhanced lipogenetic activity. On the other hand, it causes liver triglycerides accumulation, probably as a result of the decreased rate of triglycerides released into circulation, and these changes are not caused by the reduced food intake of the animals.

[Etiology of community-acquired pneumonia in ambulatory patients. Usefulness of a diagnostic investigation protocol using detection of Streptococcus pneumoniae and Legionella pneumophila antigens in urine samples]. / Etiología de la neumonía adquirida en la comunidad tratada ambulatoriamente. Utilidad de un protocolo diagnóstico con pruebas microbiológicas convencionales y detección de antígenos de Streptococcus pneumoniae y Legionella pneumophila en orina.

BACKGROUND: To determine the etiology of community-acquired pneumonia (CAP) in ambulatory patients and to assess the efficiency of a diagnostic protocol by using tests to detect bacterial antigens in urine samples. PATIENTS AND METHOD: One-year prospective study that included blood and sputum cultures, serologic studies, and detection of Legionella pneumophila and Streptococcus pneumoniae urinary antigens. RESULTS: 49 patients were recruited and an etiological diagnosis was attained in 34 (69%). Microorganisms most frequently isolated were S. pneumoniae (12 cases), Mycoplasma pneumoniae (7), Haemophilus influenzae (4), respiratory viruses (4) and Coxiella burnetii (3 cases). CONCLUSIONS: By means of a non-invasive protocol with urinary antigen tests, a microbial etiology can be established in two thirds of patients with mild CAP. S. pneumoniae is the main cause of mild CAP.

[Epidemiology of yeast colonization and oropharyngeal infection other than Candida albicans in patients with HIV infection]. / Epidemiología de la colonización e infección orofaríngea por levaduras diferentes de Candida albicans en los pacientes con infección por el VIH.

BACKGROUND: An increasing frequency of opportunistic fungal infections in immunosuppressed patients in recent years. Concurrent with this finding, it has been noted an increasing use of fluconazole. In addition, non-Candida albicans species (NCAS), most of which are fluconazole-resistant have been increasing isolated. The aim of this study was to investigate the epidemiology of colonization and infection due to NCAS in HIV-infected patients. PATIENTS AND METHODS: A cross sectional study was conducted with HIV-infected patients in different stages, who were attended at two hospitals in Alicante, Spain. We assessed the prevalence and microbiology of oropharyngeal colonization and infection due to Candida spp., and its fluconazole susceptibility patterns. To determine the clinical risk factors for the development of fluconazole resistance, we carried out a case-control study with prevalent cases. RESULTS: We studied 168 strains from 153 patients. NCAS were isolated in 32 (21%) of them, 25 (77%) were colonized, and 5 (26%) had infection due to NCAS. The most common isolate was Candida glabrata (n = 15). MICs were significantly higher for NCAS than for Candida albicans species, with a MIC50 of 16 and 0.25 microgram/ml, respectively, and a MIC90 of 128 micrograms/ml and 8 micrograms/ml (p = 0.0001). The median CD4 cell count in patients with NCAS was 0.06 x 10(9)/l, and 0.19 x 10(9)/l patients with Candida albicans (p = 0.009). Overall, 56% of the patients with NCAS and 41% of the patients with Candida albicans had been treated with fluconazole (p = 0.1). CONCLUSIONS: NCAS are isolated in a high proportion of HIV infected patients. Most of the NCAS have a decreased susceptibility to fluconazole. The only risk factor associated with the acquisition of NCAS in HIV-infected patients is an advanced immunosuppression.

[Pulmonary lymphangioleiomyomatosis. Description and course of 2 cases]. / Linfangioleiomiomatosis pulmonar. Descripción y evolución de dos casos.

Pulmonary lymphangioleiomyomatosis (LAM) is a rare, serious, chronic disease whose etiology is unknown and which affects young women almost exclusively. It produces typical clinical and radiological characteristics. Diagnosis is confirmed on finding histological evidence of irregular proliferation of the smooth muscle cells of the lungs. Treatment is not usually effective and there is rapid worsening of the pulmonary function leading to serious respiratory failure which often results in the patients death. We present two cases of LAM in women, one of whom was 33 and the other 38. In the first case the patient had all the pulmonary findings described in the literature, while the second also had bilateral renal angiomyolipomas. We discuss the histological, radiological and clinical characteristics and evolution of both cases, as well as the treatment given. We also review the literature. It is concluded that LAM should be suspected in young women who have dyspnea, cough and/or hemoptysis and an interstitial radiological pattern, especially when associated with a pleural effusion or pneumothorax.

[Leydig cell tumor, gynecomastia, and inferior vena cava thrombosis]. / Tumor de células de Leydig, ginecomastia y trombosis de vena cava inferior.

Leydig cell tumor is a testicular tumor with a low incidence characterized by a high estrogens secretion from the tumoral cells. Its more frequent clinical presentation is a testicular nodule with or without other endocrine manifestations due to estrogenic hypersecretion. We're reporting a case of a Leydig cell tumor with high plasmatic levels of estradiol, gynecomastia and inferior cava vein thrombosis, which hasn't been described among its clinical features up to now. Vascular thrombotic phenomenons have already been reported in other clinical situations with hiperestrogesism and they could also be associated with these tumors. Patients with Leydig cell tumors could be at a higher risk of developing thromboembolic phenomenons because of tumoral hyperestrogenism and could present thrombotic complications among the clinical findings.

Hormone-sensitive lipase deficiency disturbs the fatty acid composition of mouse testis.

Hormone-sensitive lipase (HSL) is a key enzyme in the mobilization of fatty acids from intracellular stores. In mice, HSL deficiency results in male sterility caused by a major defect in spermatogenesis. The testes contain high concentrations of PUFA and specific PUFA are essential for spermatogenesis. We investigated the fatty acid composition and the mRNA levels of key enzymes involved in fatty acid metabolism in testis of HSL-knockout mice. HSL deficiency altered fatty acid composition in the testis but not in plasma. The most important changes were decreases in the essential n-6 PUFA LNA and the n-3 PUFA ALA, and an increase in the corresponding synthesis intermediates C22:4n-6 and C22:5n-3 without changes in DPAn-6 or DHA acids. Mead acid, which has been associated with an essential fatty acid deficit leading to male infertility, was increased in the testis from HSL-knockout mice. Moreover, the expression of SCD-1, FADS1, and FADS2 was increased while expression of ELOVL2, an essential enzyme for the formation of very-long PUFA in testis, was decreased. Given the indispensability of these fatty acids for spermatogenesis, the changes in fatty acid metabolism observed in testes from HSL-knockout male mice may underlie the infertility of these animals.

Haloperidol disrupts lipid rafts and impairs insulin signaling in SH-SY5Y cells.

Haloperidol exerts its therapeutic effects basically by acting on dopamine receptors. We previously reported that haloperidol inhibits cholesterol biosynthesis in cultured cells. In the present work we investigated its effects on lipid-raft composition and functionality. In both neuroblastoma SH-SY5Y and promyelocytic HL-60 human cell lines, haloperidol inhibited cholesterol biosynthesis resulting in a decrease of the cell cholesterol content and the accumulation of different sterol intermediates (7-dehydrocholesterol, zymostenol and cholesta-8,14-dien-3beta-ol) depending on the dose of the drug. As a consequence, the cholesterol content in lipid rafts was greatly reduced, and several pre-cholesterol sterols, particularly cholesta-8,14-dien-3beta-ol, were incorporated into the cell membrane. This was accompanied by the disruption of lipid rafts, with redistribution of flotillin-1 and Fyn and the impairment of insulin-Akt signaling. Supplementing the medium with free cholesterol abrogated the effects of haloperidol on lipid-raft composition and functionality. LDL (low-density lipoprotein), a physiological vehicle of cholesterol in plasma, was much less effective in preventing the effects of haloperidol, which is attributed to the drug's inhibition of intracellular vesicular trafficking. These effects on cellular cholesterol homeostasis that ultimately result in the alteration of lipid-raft-dependent insulin signaling action may underlie some of the metabolic effects of this widely used antipsychotic.