Effects of medical therapy, alcohol, smoking, and endocrine disruptors on male infertility

Infertility affects up to 15% of the sexually active population, and in 50% of cases, a male factor is involved, either as a primary problem or in combination with a problem in the female partner. Because many commonly encountered drugs and medications can have a detrimental effect on male fertility, the medical evaluation should include a discussion regarding the use of recreational and illicit drugs, medications, and other substances that may impair fertility. With the knowledge of which drugs and medications may be detrimental to fertility, it may be possible to modify medication regimens or convince a patient to modify habits to decrease adverse effects on fertility and improve the chances of achieving a successful pregnancy. Concern is growing that male sexual development and reproduction have changed for the worse over the past 30 to 50 years. Although some reports find no changes, others suggest that sperm counts appear to be decreasing and that the incidence of developmental abnormalities such as hypospadias and cryptorchidism appears to be increasing, as is the incidence of testicular cancer. These concerns center around the possibility that our environment is contaminated with chemicals - both natural and synthetic - that can interact with the endocrine system.

Interferentes endócrinos no ambiente

Although the hypothesis that environmental chemicals may exhibit endocrine disrupting effects is not new, the issue has been a growing level of concern due to reports of increased incidences of endocrine-related disease in humans, including declining male fertility, and more significantly, to adverse physiological effects observed in wildlife where cause and effect relationships are more evident. The list of endocrine disrupting chemicals (EDCs) includes a range of anthropogenic compounds, phytoestrogens, naturally occurring sex steroids and synthetic estrogens. Within the aquatic environment, the presence of EDCs has concerned many scientists and water quality regulators. Discharge of effluents from treatment facilities is likely to be a significant source of input of contaminants to many systems, and the potential for concentration of hydrophilic compounds and transformation products within sludges has implications for their disposal. Then, understanding the processes and the fate of EDCs on the environment, as well as the mechanisms of endocrine disruption, may facilitate controlling or limiting exposure of both humans and the environment to these compounds.

Biodegradação de alcoóis, ftalatos e adipatos em um solo tropical contaminado

The adipic and phthalic acid esters are plasticizers, have low water solubility, high partition octanol/water coefficients (Kow) and accumulate in soil and sediments. These compounds are considered teratogenic, carcinogenic and endocrine disruptors chemicals. This study evaluated the bioremediation of tropical soil contaminated with plasticizers process wastes, in aerobic conditions, with and without introduction of acclimated bacteria. It was selected 200 kg of contaminated tropical soil for the biodegradation study. The plasticizers concentrations in soil ranged between 153 mgDOA/kg up to 15552 mgDIDP/kg and after 90 days of biodegradation, the lower removal efficiencies were 72% with a 1-2 log simultaneous bacterial growth.

Determinação de plastificantes em água potável utilizando cromatografia gasosa e espectrometria de massas

This study investigated the levels of plasticizer endocrine disruptors (diethyl phthalate, dibutyl phthalate, and bisphenol A) in drinking water at Paraíba do Sul River region and release of these compounds from bottled water. An analytical method employing solid phase extraction and GC/MS was optimized and validated. The results showed that the method is selective, linear (r² > 0.99), precise (RSD <12%), accurate (recoveries between 62 and 105%), sensitive and robust. Applying the method, the presence of all studied pollutants in drinking water was observed for the three sampled plasticizers. These plasticizers were not found in mineral bottled water, before or after storage.

Avaliação da remoção de fármacos e de desreguladores endócrinos em águas de abastecimento por clarificação em escala de bancada

In this work, the efficiency of clarification treatment (coagulation, flocculation and sedimentation) with polyaluminum chloride (PAC) and aluminum sulfate (SA) as coagulants was evaluated in the removal of 7 microcontaminants (diclofenac - DCF, sulfamethoxazole - SMX, ethinylestradiol - EE2, bisphenol-A - BPA, estradiol - E2, estrone - E1 and estriol - E3) in water of low and high turbidity. The clarification treatment led to poor removal rates (40% at most) for all microcontaminants except SMX which exhibited intermediate removal efficiency (67 to 70%). Overall, PAC application yielded better performance compared to SA.

Surgical treatment of endocrine exophthalmos by removal of orbital fat: clinical experience

PURPOSE: To report a series of 73 patients with endocrine exophthalmos treated by removal of orbital fat using the transpalpebral approach during the period 1989 to 1999. METHODS: The operation was performed according to the technique described by Olivari. Aesthetic analysis was done preoperatively and postoperatively (more than 6 months after surgery). The number of complications was also observed. RESULTS: The average volume of resected fat was approximately 7.6 mL per orbit. No major complication was observed. In 9 patients with epiphora, all improved. One patient developed postoperative diplopia and 5 complained of temporary diplopia. Appearance improved in 62 patients (85%). CONCLUSION: Surgical removal of orbital fat associated with endocrine exophthalmos provides consistent improvement in appearance with a low rate of complications. Additional procedures may be indicated to improve the cosmetic outcome.

Secretory activity and endocrine regulation of male accessory glands in the blood-sucking bug Panstrongylus megistus (Hemiptera: Reduviidae)

The epithelial cells of Panstrongylus megistus male accessory glands (MAG) present ultrastructural characteristics of a secretory cell. Their secretory products are accumulated in the lumen of the four MAG lobes. During the first 8 days of adult life a strong secretion activity occurs, accumulating enough material to produce the first spermatophore. Cerebral neurosecretions as well as juvenile hormone are both involved in MAG secretory activity regulation. Juvenile hormone seems to be the responsible for the stimulation of most protein synthesis in male accessory glands. Cerebral neurosecretion seems to be necessary to stimulate juvenile hormone production and release by the corpus allatum. Furthermore, neurosecretion is required for some polypeptides synthesis by MAG. Although topic application of precocene II to adult males does not reproduce the same effects on MAG as does allatectomy, this compound causes strong reduction on male reproductive capacity.

The influence of selected pathological states on the somatostatin-like immunoreactive (SOM-LI) endocrine cells in the mucosal layer of the porcine descending colon

This study reports on changes in the number of somatostatin-like immunoreactive (SOM-LI) endocrine cells in the porcine descending colon, caused by chemically driven inflammation, axotomy and proliferative enteropathy (PE). The distribution pattern of SOM-LI endocrine cells has been studied using the routine single-labelling immunofluorescence technique. Semi-quantitative evaluation of the number of the SOM-immunostained endocrine cells within the mucosal layer of the porcine descending colon has been based on counting of all endocrine cells immunoreactive to SOM per unit area (0,1 mm²). Under physiological conditions the number of SOM-LI endocrine cells has been shown to constitute 3,30±0,22. All applied pathological processes resulted in changes in the SOM-like immunoreactivity, which varied in particular processes studied. The number of SOM-LI endocrine cells increased to 6,28±0,31 and 4,43±0,35 during chemically driven inflammation and proliferative enteropathy, respectively, and decreased to 1,17%±0,16 after axotomy. The obtained results suggest that SOM-LI endocrine cells may participate in various pathological states within porcine descending colon and their functions probably depend on the type of pathological factor.

The neuroimmune-endocrine axis: pathophysiological implications for the central nervous system cytokines and hypothalamus-pituitary-adrenal hormone dynamics

Cytokines are molecules that were initially discovered in the immune system as mediators of communication between various types of immune cells. However, it soon became evident that cytokines exert profound effects on key functions of the central nervous system, such as food intake, fever, neuroendocrine regulation, long-term potentiation, and behavior. In the 80's and 90's our group and others discovered that the genes encoding various cytokines and their receptors are expressed in vascular, glial, and neuronal structures of the adult brain. Most cytokines act through cell surface receptors that have one transmembrane domain and which transduce a signal through the JAK/STAT pathway. Of particular physiological and pathophysiological relevance is the fact that cytokines are potent regulators of hypothalamic neuropeptidergic systems that maintain neuroendocrine homeostasis and which regulate the body's response to stress. The mechanisms by which cytokine signaling affects the function of stress-related neuroendocrine systems are reviewed in this article.

Lack of mutations of exon 2 of the MEN1 gene in endocrine and nonendocrine sporadic tumors

In addition to the mutations that underlie most cases of the multiple endocrine neoplasia type 1 (MEN1) syndrome, somatic mutations of the MEN1 gene have also been described in sporadic tumors like gastrinomas, insulinomas and bronchial carcinoid neoplasm. We examined exon 2 of this gene, where most of the mutations have been described, in 148 endocrine and nonendocrine sporadic tumors. DNA was obtained by phenol/chloroform extraction and ethanol precipitation from 92 formalin-fixed, paraffin-embedded samples, and from 40 fresh tumor tissue samples. We used 5 pairs of primers to encompass the complete coding sequence of exon 2 of the MEN1 gene that was screened by the polymerase chain reaction-single-stranded conformation polymorphism (PCR-SSCP) technique in 78 sporadic thyroid cancers: 28 follicular adenomas, 35 papillary carcinomas, 14 follicular carcinomas, and 1 anaplastic thyroid carcinoma. We also examined 46 adrenal lesions (3 hyperplasias, 3 adenomas and 35 adrenocortical carcinomas, 2 pheochromocytomas, 2 ganglioneuroblastomas, and 1 lymphoma) and 24 breast cancers (6 noninvasive, 16 infiltrating ductal, and 2 invasive lobular tumors). The PCR product of 5 tumors suspected to present band shifts by SSCP was cloned. Direct sense and antisense sequencing did not identify mutations. These results suggest that the MEN1 gene is not important in breast, thyroid or adrenal sporadic tumorigenesis. Because the frequency of mutations varies significantly among tumor subgroups and allelic deletions are frequently observed at 11q13 in thyroid and adrenal cancers, another tumor suppressor gene residing in this region is likely to be involved in the tumorigenesis of these neoplasms.

Effects of sedation during upper gastrointestinal endoscopy on endocrine response and cardiorespiratory function

Upper gastrointestinal endoscopy is often accompanied by tachycardia which is known to be an important pathogenic factor in the development of myocardial ischemia. The pathogenesis of tachycardia is unknown but the condition is thought to be due to the endocrine response to endoscopy. The purpose of the present study was to investigate the effects of sedation on the endocrine response and cardiorespiratory function. Forty patients scheduled for diagnostic upper gastrointestinal endoscopy were randomized into 2 groups. While the patients in the first group did not receive sedation during upper gastrointestinal endoscopy, the patients in the second group were sedated with intravenous midazolam at the dose of 5 mg for those under 65 years or 2.5 mg for those aged 65 years or more. Midazolam was administered by slow infusion. In both groups, blood pressure, ECG tracing, heart rate, and peripheral oxygen saturation (SpO2) were monitored during endoscopy. In addition, blood samples for the determination of cortisol, glucose and C-reactive protein levels were obtained from patients in both groups prior to and following endoscopy. Heart rate and systolic arterial pressure changes were within normal limits in both groups. Comparison of the two groups regarding the values of these two parameters did not reveal a significant difference, while a statistically significant reduction in SpO2 was found in the sedation group. No significant differences in serum cortisol, glucose or C-reactive protein levels were observed between the sedated and non-sedated group. Sedation with midazolam did not reduce the endocrine response and the tachycardia developing during upper gastrointestinal endoscopy, but increased the reduction in SpO2.

Endothelial dysfunction in cardiovascular and endocrine-metabolic diseases: an update

The endothelium plays a vital role in maintaining circulatory homeostasis by the release of relaxing and contracting factors. Any change in this balance may result in a process known as endothelial dysfunction that leads to impaired control of vascular tone and contributes to the pathogenesis of some cardiovascular and endocrine/metabolic diseases. Reduced endothelium-derived nitric oxide (NO) bioavailability and increased production of thromboxane A2, prostaglandin H2 and superoxide anion in conductance and resistance arteries are commonly associated with endothelial dysfunction in hypertensive, diabetic and obese animals, resulting in reduced endothelium-dependent vasodilatation and in increased vasoconstrictor responses. In addition, recent studies have demonstrated the role of enhanced overactivation ofβ-adrenergic receptors inducing vascular cytokine production and endothelial NO synthase (eNOS) uncoupling that seem to be the mechanisms underlying endothelial dysfunction in hypertension, heart failure and in endocrine-metabolic disorders. However, some adaptive mechanisms can occur in the initial stages of hypertension, such as increased NO production by eNOS. The present review focuses on the role of NO bioavailability, eNOS uncoupling, cyclooxygenase-derived products and pro-inflammatory factors on the endothelial dysfunction that occurs in hypertension, sympathetic hyperactivity, diabetes mellitus, and obesity. These are cardiovascular and endocrine-metabolic diseases of high incidence and mortality around the world, especially in developing countries and endothelial dysfunction contributes to triggering, maintenance and worsening of these pathological situations.

Development of the endocrine pancreas and novel strategies for β-cell mass restoration and diabetes therapy

Diabetes mellitus represents a serious public health problem owing to its global prevalence in the last decade. The causes of this metabolic disease include dysfunction and/or insufficient number of β cells. Existing diabetes mellitus treatments do not reverse or control the disease. Therefore, β-cell mass restoration might be a promising treatment. Several restoration approaches have been developed: inducing the proliferation of remaining insulin-producing cells, de novo islet formation from pancreatic progenitor cells (neogenesis), and converting non-β cells within the pancreas to β cells (transdifferentiation) are the most direct, simple, and least invasive ways to increase β-cell mass. However, their clinical significance is yet to be determined. Hypothetically, β cells or islet transplantation methods might be curative strategies for diabetes mellitus; however, the scarcity of donors limits the clinical application of these approaches. Thus, alternative cell sources for β-cell replacement could include embryonic stem cells, induced pluripotent stem cells, and mesenchymal stem cells. However, most differentiated cells obtained using these techniques are functionally immature and show poor glucose-stimulated insulin secretion compared with native β cells. Currently, their clinical use is still hampered by ethical issues and the risk of tumor development post transplantation. In this review, we briefly summarize the current knowledge of mouse pancreas organogenesis, morphogenesis, and maturation, including the molecular mechanisms involved. We then discuss two possible approaches of β-cell mass restoration for diabetes mellitus therapy: β-cell regeneration and β-cell replacement. We critically analyze each strategy with respect to the accessibility of the cells, potential risk to patients, and possible clinical outcomes.

Ill-defined causes of death in Brazil: a redistribution method based on the investigation of such causes

OBJECTIVE To propose a method of redistributing ill-defined causes of death (IDCD) based on the investigation of such causes.METHODS In 2010, an evaluation of the results of investigating the causes of death classified as IDCD in accordance with chapter 18 of the International Classification of Diseases (ICD-10) by the Mortality Information System was performed. The redistribution coefficients were calculated according to the proportional distribution of ill-defined causes reclassified after investigation in any chapter of the ICD-10, except for chapter 18, and used to redistribute the ill-defined causes not investigated and remaining by sex and age. The IDCD redistribution coefficient was compared with two usual methods of redistribution: a) Total redistribution coefficient, based on the proportional distribution of all the defined causes originally notified and b) Non-external redistribution coefficient, similar to the previous, but excluding external causes.RESULTS Of the 97,314 deaths by ill-defined causes reported in 2010, 30.3% were investigated, and 65.5% of those were reclassified as defined causes after the investigation. Endocrine diseases, mental disorders, and maternal causes had a higher representation among the reclassified ill-defined causes, contrary to infectious diseases, neoplasms, and genitourinary diseases, with higher proportions among the defined causes reported. External causes represented 9.3% of the ill-defined causes reclassified. The correction of mortality rates by the total redistribution coefficient and non-external redistribution coefficient increased the magnitude of the rates by a relatively similar factor for most causes, contrary to the IDCD redistribution coefficient that corrected the different causes of death with differentiated weights.CONCLUSIONS The proportional distribution of causes among the ill-defined causes reclassified after investigation was not similar to the original distribution of defined causes. Therefore, the redistribution of the remaining ill-defined causes based on the investigation allows for more appropriate estimates of the mortality risk due to specific causes.

Hyponatremia in visceral leishmaniasis

There are few reports linking hyponatremia and visceral leishmaniasis (kala-azar). This is a study of 55 consecutive kala-azar patients and 20 normal individuals as a control group. Hyponatremia and serum hypo-osmolality were detected in 100% of kala-azar patients. High first morning urine osmolality (750.0 ± 52.0 vs. 894.5 ± 30.0mOsm/kg H2O, p < 0.05), and high 24-hour urine osmolality (426.0 ± 167.0 vs. 514.6 ± 132.0 mOsm/kg H2O, p < 0.05) demonstrated persistent antidiuretic hormone secretion. Urinary sodium was high (82.3 ± 44.2 vs.110.3 ± 34.7 mEq/L, p < 0.05). Low seric uric acid occurred in 61.8% of patients and increased fractional urinary uric acid excretion was detected in 74.5% of them. Increased glomerular filtration rate was present in 25.4% of patients. There was no evidence of extracellular volume depletion. Normal plasma ADH levels were observed in kala-azar patients. No endocrine or renal dysfunction was detected. It is possible that most hyponatremic kala-azar patients present the syndrome of inappropriate antidiuretic hormone secretion.