Skeletal Muscle Na+ Channel Disorders

Five inherited human disorders affecting skeletal muscle contraction have been traced to mutations in the gene encoding the voltage-gated sodium channel Nav1.4. The main symptoms of these disorders are myotonia or periodic paralysis caused by changes in skeletal muscle fiber excitability. Symptoms of these disorders vary from mild or latent disease to incapacitating or even death in severe cases. As new human sodium channel mutations corresponding to disease states become discovered, the importance of understanding the role of the sodium channel in skeletal muscle function and disease state grows

MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis.

The subthreshold, voltage-gated potassium channel of skeletal muscle is shown to contain MinK-related peptide 2 (MiRP2) and the pore-forming subunit Kv3.4. MiRP2-Kv3.4 channels differ from Kv3.4 channels in unitary conductance, voltage-dependent activation, recovery from inactivation, steady-state open probability, and block by a peptide toxin. Thus, MiRP2-Kv3.4 channels set resting membrane potential (RMP) and do not produce afterhyperpolarization or cumulative inactivation to limit action potential frequency. A missense mutation is identified in the gene for MiRP2 (KCNE3) in two families with periodic paralysis and found to segregate with the disease. Mutant MiRP2-Kv3.4 complexes exhibit reduced current density and diminished capacity to set RMP. Thus, MiRP2 operates with a classical potassium channel subunit to govern skeletal muscle function and pathophysiology

Lifestyle factors and breast cancer in a Moroccan population case-control study of the center Mohammed VI for cancer treatment

Background: The study aims to examine the association between lifestyle habits and breast cancer risk in a Moroccan population.Methods: This is a case-control study conducted at the Mohammed VI Centre for cancer treatment in Casablanca.Results: The results highlighted that family history of breast cancer (OR=5.73) and alcohol consumption                     (OR=3.76) were positively associated with breast cancer. Analysis of anthropometric parameters showed that the risk of developing breast cancer is estimated at 1.78 in overweight women and 2.39 in obese women compared to those of normal weight. The risk of developing breast cancer is estimated at 1.82 for women with a WC greater than 88 cm and 1.70 for women with a WHR greater than 0.85. At age 10, the risk is 1.60 for women with a large figure compared to women with a small figure. However, at age 40, the average body shape relative to the lean body was associated with a decreased risk of breast cancer. In addition, the data confirmed that physical activity participation decreases with age; in childhood and adolescence, women are more active while in post-menopause, women become moderately active. Being very active in childhood, peri-menopause and post-menopause seems to be a protective factor against the occurrence of breast cancer.Conclusions: The study showed that the risk of breast cancer is potentially high in elderly women, overweight women and women with a family history of cancer. This risk was increased by behavioral factors such as toxic habits and physical inactivity

Sociodemographic factors and delay in the diagnosis of cervical cancer in Morocco

Background: In Morocco, cervical cancer is the second most common cancer in women. The cases of cervical cancer are diagnosed at a late stage: 43.7% presented at stage II of diagnosis (FIGO) and 38.1% in advanced stage (stage III and IV). The main objective of this study is to investigate factors associated to late the diagnosis of cervical cancer in Morocco as measured by the stage at diagnosis and delays between first symptoms and diagnosis of cancer. Methods: Cross-sectional studies, conducted from June-2008 to June-2010 at two main oncological centers. Two-hundred cases were recruited. Stages I & II were identified as "early-stage". The dates of first-symptoms, first-consultation and first-diagnosis were used to define "Patient", "Medical" and "Total" delays. Results: Elevated risks for late stage was observed for women unmarried (OR=5.0; 95%CI: 1.43-16.66); living > 100 km from center of diagnosis (OR=4.51; 95%CI: 1.35-15.11); without a familial history of cancer (OR=14.28; 95%CI: 2.22-100) and whose was the first symptom not bleeding (OR=25; 95%CI: 1.62-300). Frequency of housewives was significantly higher for women with a "patient-delay. ≥1 month. Frequency of patients who had symptoms of .bleeding. was significantly higher for women with a "patient-delay" <1 month. Frequency of patients from urban area was significantly higher for women with a "Medical-delay" < 1 month. Elevated risks for a long "Total-delay" was observed for women aged < 50 years (OR=2.44; 95%CI: 1.24-4.76); illiterate (OR=3.85; 95%CI: 1.45-10.00) and from rural-area (OR=2.56; 95%CI: 1.25-5.26). Conclusion: Our results may represent an important tool in guiding the actions for an early diagnosis of cervical cancer. Pan African Medical Journal 2012; 12:1

Acoustic assessment of erygmophonic speech of Moroccan laryngectomized patients

Introduction: Acoustic evaluation of alaryngeal voices is among the most prominent issues in speech analysis field. In fact, many methods have been developed to date to substitute the classic perceptual evaluation. The Aim of this study is to present our experience in erygmophonic speech objective assessment and to discuss the most widely used methods of acoustic speech appraisal. through a prospective case-control study we have measured acoustic parameters of speech quality during one year of erygmophonic rehabilitation therapy of Moroccan laryngectomized patients. Methods: We have assessed acoustic parameters of erygmophonic speech samples of eleven laryngectomized patients through the speech rehabilitation therapy. Acoustic parameters were obtained by perturbation analysis method and linear predictive coding algorithms also through the broadband spectrogram. Results: Using perturbation analysis methods, we have found erygmophonic voice to be significantly poorer than normal speech and it exhibits higher formant frequency values. However, erygmophonic voice shows also higher and extremely variable Error values that were greater than the acceptable level. And thus, live a doubt on the reliability of those analytic methods results. Conclusion: Acoustic parameters for objective evaluation of alaryngeal voices should allow a reliable representation of the perceptual evaluation of the quality of speech. This requirement has not been fulfilled by the common methods used so far. Therefore, acoustical assessment of erygmophonic speech needs more investigations

An atypical phenotype of hypokalemic periodic paralysis caused by a mutation in the sodium channel gene SCN4A

Familial hypokalemic periodic paralysis is an autosomal-dominant channelopathy characterized by episodic muscle weakness with hypokalemia. The respiratory and cardiac muscles typically remain unaffected, but we report an atypical case of a family with hypokalemic periodic paralysis in which the affected members presented with frequent respiratory insufficiency during severe attacks. Molecular analysis revealed a heterozygous c.664 C>T transition in the sodium channel gene SCN4A, leading to an Arg222Trp mutation in the channel protein. The patients described here presented unusual clinical characteristics that included a severe respiratory phenotype, an incomplete penetrance in female carriers, and a different response to medications

Hypokalemic periodic paralysis; two different genes responsible for similar clinical manifestations

Primary hypokalemic periodic paralysis (HOKPP) is an autosomal dominant disorder manifesting as recurrent periodic flaccid paralysis and concomitant hypokalemia. HOKPP is divided into type 1 and type 2 based on the causative gene. Although 2 different ion channels have been identified as the molecular genetic cause of HOKPP, the clinical manifestations between the 2 groups are similar. We report the cases of 2 patients with HOKPP who both presented with typical clinical manifestations, but with mutations in 2 different genes (CACNA1Sp.Arg528His and SCN4A p.Arg672His). Despite the similar clinical manifestations, there were differences in the response to acetazolamide treatment between certain genotypes of SCN4A mutations and CACNA1S mutations. We identified p.Arg672His in the SCN4A gene of patient 2 immediately after the first attack through a molecular genetic testing strategy. Molecular genetic diagnosis is important for genetic counseling and selecting preventive treatment

Assessment of Trace Metals in Sediments from Khnifiss Lagoon (Tarfaya, Morocco)

Surface sediments from Khnifiss lagoon (Morocco) were analyzed to evaluate the contamination degree of the area. Concentrations of V, Cr, Co, Ni, Cu, Zn, As, Cd, Hg, and Pb were determined on samples taken during the summer and the autumn of 2016. On the whole, higher concentrations were found in the summer season. The results revealed the following average concentrations (mg/kg), reported in descending order: Zn (51.7 ± 31.3) > V (38.8 ± 24.7) > Cr (26.6 ± 17.8) > Ni (16.5 ± 5.47) > As (8.50 ± 2.00) > Cu (6.60 ± 3.81) > Pb (6.13 ± 3.46) > Co (3.57 ± 2.09) > Cd (0.16 ± 0.11) > Hg (0.006 ± 0.001). Organic matter showed a positive significant correlation with some trace metals (mainly V, Cr, Co, Zn, Cd, Pb). Three pollution indices were calculated: Enrichment Factor (EF), Index of Geo−accumulation (Igeo), and Pollution Load Index (PLI). Minimal enrichments (for Zn, As, and Cd) were detected at some sampling points. Overall indices showed that the Khnifiss sediments can be classified as not contaminated, and that the trace metals amounts found are ascribable to the geogenic origin. The results of this work can be used as a starting point for further evaluations of trace metals distribution in Moroccan lagoons