Prevalence of the A1555G (12S rRNA) and tRNA Ser(UCN) mitochondrial mutations in hearing-impaired Brazilian patients

Mitochondrial mutations are responsible for at least 1% of the cases of hereditary deafness, but the contribution of each mutation has not yet been defined in African-derived or native American genetic backgrounds. A total of 203 unselected hearing-impaired patients were screened for the presence of the mitochondrial mutation A1555G in the 12S rRNA gene and mutations in the tRNA Ser(UCN) gene in order to assess their frequency in the ethnically admixed Brazilian population. We found four individuals with A1555G mutation (2%), which is a frequency similar to those reported for European-derived populations in unselected samples. On the other hand, complete sequencing of the tRNA Ser(UCN) did not reveal reported pathogenic substitutions, namely A7445G, 7472insC, T7510C, or T7511C. Instead, other rare substitutions were found such as T1291C, A7569G, and G7444A. To evaluate the significance of these findings, 110 "European-Brazilians" and 190 "African-Brazilians" unrelated hearing controls were screened. The T1291C, A7569G and G7444A substitutions were each found in about 1% (2/190) of individuals of African ancestry, suggesting that they are probably polymorphic. Our results indicate that screening for the A1555G mutation is recommended among all Brazilian deaf patients, while testing for mutations in the tRNA Ser(UCN) gene should be considered only when other frequent deafness-causing mutations have been excluded or in the presence of a maternal transmission pattern.

Sleep disorders, sleepiness and traffic safety: a public health menace

Sleep disorders are not uncommon and have been widely reported throughout the world. They have a profound impact on industrialized 24-h societies. Consequences of these problems include impaired social and recreational activities, increased human errors, loss of productivity, and elevated risk of accidents. Conditions such as acute and chronic insomnia, sleep loss, excessive sleepiness, shift-work, jet lag, narcolepsy, and sleep apnea warrant public health attention, since residual sleepiness during the day may affect performance of daily activities such as driving a car. Benzodiazepine hypnotics and zopiclone promote sleep, both having residual effects the following day including sleepiness and reduced alertness. In contrast, the non-benzodiazepine hypnotics zolpidem and zaleplon have no significant next-day residual effects when taken as recommended. Research on the effects of wakefulness-promoting drugs on driving ability is limited. Countermeasures for excessive daytime sleepiness have a limited effect. There is a need for a social awareness program to educate the public about the potential consequences of various sleep disorders such as narcolepsy, sleep apnea, shift-work-related sleep loss, and excessive daytime sleepiness in order to reduce the number of sleep-related traffic accidents.

Immunoglobulin production is impaired in protein-deprived mice and can be restored by dietary protein supplementation

Most contacts with food protein and microbiota antigens occur at the level of the gut mucosa. In animal models where this natural stimulation is absent, such as germ-free and antigen-free mice, the gut-associated lymphoid tissue (GALT) and systemic immunological activities are underdeveloped. We have shown that food proteins play a critical role in the full development of the immune system. C57BL/6 mice weaned to a diet in which intact proteins are replaced by equivalent amounts of amino acids (Aa diet) have a poorly developed GALT as well as low levels of serum immunoglobulins (total Ig, IgG, and IgA, but not IgM). In the present study, we evaluated whether the introduction of a protein-containing diet in 10 adult Aa-fed C57BL/6 mice could restore their immunoglobulin levels and whether this recovery was dependent on the amount of dietary protein. After the introduction of a casein-containing diet, Aa-fed mice presented a fast recovery (after 7 days) of secretory IgA (from 0.33 to 0.75 mg/mL, while in casein-fed mice this value was 0.81 mg/mL) and serum immunoglobulin levels (from 5.39 to 10.25 mg/mL of total Ig). Five percent dietary casein was enough to promote the restoration of secretory IgA and serum immunoglobulin levels to a normal range after 30 days feeding casein diet (as in casein-fed mice - 15% by weight of diet). These data suggest that the defect detected in the immunoglobulin levels was a reversible result of the absence of food proteins as an antigenic stimulus. They also indicate that the deleterious consequences of malnutrition at an early age for some immune functions may be restored by therapeutic intervention later in life.

Roles of calcium and IP3 in impaired colon contractility of rats following multiple organ dysfunction syndrome

The purpose of the present study was to explore changes in rat colon motility, and determine the roles of calcium and inositol (1,4,5)-triphosphate (IP3) in colon dysmotility induced by multiple organ dysfunction syndrome (MODS) caused by bacteria peritonitis. The number of stools, the contractility of the muscle strips and the length of smooth muscle cells (SMC) in the colon, the concentration of calcium and IP3 in SMC, and serum nitric oxide were measured. Number of stools, fecal weight, IP3 concentration in SMC and serum nitric oxide concentration were 0.77 ± 0.52 pellets, 2.51 ± 0.39 g, 4.14 ± 2.07 pmol/tube, and 113.95 ± 37.89 µmol/L, respectively, for the MODS group (N = 11) vs 1.54 ± 0.64 pellets, 4.32 ± 0.57 g, 8.19 ± 3.11 pmol/tube, and 37.42 ± 19.56 µmol/L for the control group (N = 20; P < 0.05). After treatment with 0.1 mM acetylcholine and 0.1 M potassium chloride, the maximum contraction stress of smooth muscle strips, the length of SMC and the changes of calcium concentration were 593 ± 81 and 458 ± 69 g/cm³, 48.1 ± 11.8 and 69.2 ± 15.7 µM, 250 ± 70 and 167 ± 48%, respectively, for the control group vs 321 ± 53 and 284 ± 56 g/cm³, 65.1 ± 18.5 and 87.2 ± 23.7 µM, 127 ± 35 and 112 ± 35% for the MODS group (P < 0.05). Thus, colon contractility was decreased in MODS, a result possibly related to reduced calcium concentration and IP3 in SMC.

Endothelium-dependent and -independent hepatic artery vasodilatation is not impaired in a canine model of liver ischemia-reperfusion injury

We investigated whether hepatic artery endothelium may be the earliest site of injury consequent to liver ischemia and reperfusion. Twenty-four heartworm-free mongrel dogs of either sex exposed to liver ischemia/reperfusion in vivo were randomized into four experimental groups (N = 6): a) control, sham-operated dogs, b) dogs subjected to 60 min of ischemia, c) dogs subjected to 30 min of ischemia and 60 min of reperfusion, and d) animals subjected to 45 min of ischemia and 120 min of reperfusion. The nitric oxide endothelium-dependent relaxation of hepatic artery rings contracted with prostaglandin F2a and exposed to increasing concentrations of acetylcholine, calcium ionophore A23187, sodium fluoride, phospholipase-C, poly-L-arginine, isoproterenol, and sodium nitroprusside was evaluated in organ-chamber experiments. Lipid peroxidation was estimated by malondialdehyde activity in liver tissue samples and by blood lactic dehydrogenase (LDH), serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) activities. No changes were observed in hepatic artery relaxation for any agonist tested. The group subjected to 45 min of ischemia and 120 min of reperfusion presented marked increases of serum aminotransferases (ALT = 2989 ± 1056 U/L and AST = 1268 ± 371 U/L; P < 0.01), LDH = 2887 ± 1213 IU/L; P < 0.01) and malondialdehyde in liver samples (0.360 ± 0.020 nmol/mgPT; P < 0.05). Under the experimental conditions utilized, no abnormal changes in hepatic arterial vasoreactivity were observed: endothelium-dependent and independent hepatic artery vasodilation were not impaired in this canine model of ischemia/reperfusion injury. In contrast to other vital organs and in the ischemia/reperfusion injury environment, dysfunction of the main artery endothelium is not the first site of reperfusion injury.

Restless leg syndrome, sleep quality and fatigue in multiple sclerosis patients

We have tested the hypothesis that restless leg syndrome (RLS) is related to quality of sleep, fatigue and clinical disability in multiple sclerosis (MS). The diagnosis of RLS used the four minimum criteria defined by the International Restless Legs Syndrome Study Group. Fatigue was assessed by the Fatigue Severity Scale (FSS >27), quality of sleep by the Pittsburgh Sleep Quality Index (PSQI >6), excessive daytime sleepiness by the Epworth Sleepiness Scale (ESS >10) and clinical disability by the Expanded Disability Status Scale (EDSS). Forty-four patients (32 women) aged 14 to 64 years (43 ± 14) with disease from 0.4 to 23 years (6.7 ± 5.9) were evaluated. Thirty-five were classified as relapsing-remitting, 5 as primary progressive and 4 as secondary progressive. EDSS varied from 0 to 8.0 (3.6 ± 2.0). RLS was detected in 12 cases (27%). Patients with RLS presented greater disability (P = 0.01), poorer sleep (P = 0.02) and greater levels of fatigue (P = 0.03). Impaired sleep was present in 23 (52%) and excessive daytime sleepiness in 3 cases (6.8%). Fatigue was present in 32 subjects (73%) and was associated with clinical disability (P = 0.000) and sleep quality (P = 0.002). Age, gender, disease duration, MS pattern, excessive daytime sleepiness and the presence of upper motor neuron signs were not associated with the presence of RLS. Fatigue was best explained by clinical disability and poor sleep quality. Awareness of RLS among health care professionals may contribute to improvement in MS management.

Raising awareness of chronic kidney disease in a Brazilian urban population

The incidence and prevalence of chronic kidney disease have been increasing in recent years in developing countries. The aim of this study was to report the results of a general chronic kidney disease awareness program applied to an urban population in a large Brazilian city. From January 2002 to January 2005 a total of 8883 individuals in the city of Curitiba (PR, Brazil) were screened for hypertension, body mass index, hematuria, and proteinuria. A family history and previous medical diagnosis of hypertension and diabetes mellitus (DM) were also recorded. Of the 8883 individuals assessed, 56% were women, subject median age was 47 years (range: 17-93 years) and more than 90% were Caucasian. Thirty percent had signs of hematuria, 6% had proteinuria, and 3% had hematuria and proteinuria. The median of mean arterial pressure values was 93 mmHg (range: 71-135 mmHg) and 16% of the population screened had a history of hypertension. A significant positive family history of both hypertension or DM was present in 42% (P < 0.0001; chi-square = 83.18) and 7% (P < 0.0001; chi-square = 161.31) of the hypertensive group, respectively. Finally, the prevalence of hypertension and DM was significantly higher in older individuals with proteinuria. In the present study, a higher prevalence of hematuria and proteinuria was found in older individuals with hypertension and diabetes compared to the general population. These data confirm the need for public awareness of renal disease in high-risk individuals.

Transplantation and survival of mouse inner ear progenitor/stem cells in the organ of Corti after cochleostomy of hearing-impaired guinea pigs: preliminary results

In mammals, damage to sensory receptor cells (hair cells) of the inner ear results in permanent sensorineural hearing loss. Here, we investigated whether postnatal mouse inner ear progenitor/stem cells (mIESCs) are viable after transplantation into the basal turns of neomycin-injured guinea pig cochleas. We also examined the effects of mIESC transplantation on auditory functions. Eight adult female Cavia porcellus guinea pigs (250-350g) were deafened by intratympanic neomycin delivery. After 7 days, the animals were randomly divided in two groups. The study group (n=4) received transplantation of LacZ-positive mIESCs in culture medium into the scala tympani. The control group (n=4) received culture medium only. At 2 weeks after transplantation, functional analyses were performed by auditory brainstem response measurement, and the animals were sacrificed. The presence of mIESCs was evaluated by immunohistochemistry of sections of the cochlea from the study group. Non-parametric tests were used for statistical analysis of the data. Intratympanic neomycin delivery damaged hair cells and increased auditory thresholds prior to cell transplantation. There were no significant differences between auditory brainstem thresholds before and after transplantation in individual guinea pigs. Some mIESCs were observed in all scalae of the basal turns of the injured cochleas, and a proportion of these cells expressed the hair cell marker myosin VIIa. Some transplanted mIESCs engrafted in the cochlear basilar membrane. Our study demonstrates that transplanted cells survived and engrafted in the organ of Corti after cochleostomy.

Microbiological quality of hamburgers sold in the streets of Cuiabá - MT, Brazil and vendor hygiene-awareness

This study evaluated the microbiological quality of hamburgers and the microbe community on the hands of vendors in Cuiabá, Mato Grosso, Brazil, in relation to vendors´ awareness as to what constitute acceptable food-handling practices as part of a broad-spectrum research programme on street foods in Brazil . Sale of the hamburger known as the 'baguncinha' is common and widespread in urban Cuiabá, Mato Grosso, Brazil. Food inspectors encounter various difficulties in carrying out inspections. One hundred and five hamburgers samples were evaluated using conventional methods including tests for facultative aerobic and/or anaerobic mesophytic bacteria, coliform counts at 45 °C, the coagulase test for Staphylococcus, Gram-staining for the presence of Bacillus cereus, Clostridium sulphite reductase and Salmonella spp. The hamburgers were categorized as unsuitable for human consumption in 31.4% of samples, with those testing positive for coliforms and Staphylococcus at unacceptably high levels by Brazilian standards. High levels of microbiological contamination were detected on the hands of the food handlers and mesophytic bacterial counts reached 1.8 × 10(4) CFU/hand. Interviews were carried out by means of questionnaires to evaluate levels of awareness as to acceptable food handling practices and it was found that 80,1% of vendors had never participated in any kind of training.