Neuropathogenesis of Multiple Sclerosis and Huntington's Disease

Substantial epidemiological studies have established a link between environmental factors and prevalence of neurodegenerative diseases. Increasingly, some studies report a direct cause-and-effect relation between environmental agents such as heavy metals and pesticides, and some neurodegenerative disorders including multiple sclerosis (MS) and Huntington's disease (HD). Interestingly, high blood level of heavy metals and pesticides has been shown in patients with MS and HD. Those agents could be involved directly or indirectly in the pathogenesis of MS and HD. The underlying mechanisms may imply an immune breaking of self-tolerance or neurodegeneration onset of several neurotransmission systems. The chapter will discuss the role of different metals and pesticides in the onset and progress of MS and HD with an overview of the possible underlying pathomechanisms.

Griscelli Syndrome Type 2: A Rare Case With Apparently Normal Skin and Hair Pigmentation

t- Griscelli syndrome (GS) is a rare autosomal recessive disease that affects hair, skin, and immune system. Here, we describe an 8.5-month-old infant with multiple admissions due to fever, petechial purpura, and several recurrent vomiting episodes with a presumptive diagnosis of recurrent sepsis. He was born from parents with consanguineous marriage. The initial examinations revealed huge splenomegaly and hepatomegaly without any source of infection. Laboratory tests revealed a hemophagocytic lymphohistiocytosis (HLH) like a picture with a high blood level of ferritin in all episodes, but the bone marrow test result was normal. Although he had normal hair and skin pigmentation on physical examination, the accumulation of melanosomes was found in his hair shafts on microscopic investigations. Eventually, a genetic test revealed a mutation in the RAB27A gene, which confirmed GS-II diagnosis. Our case is the first case of GS-II from Iran without any apparent clinical features of GS, such as hypopigmented skin and silvery-gray hair. Therefore, a genetic test, together with the microscopic examination of hair and skin, is necessary for the diagnosis and confirmation of GS-II. Since GS-II is an autosomal recessive disorder and consanguineous marriages are popular in Iran, premarital genetic counseling is recommended for this region.

Neuropathogenesis of Multiple Sclerosis and Huntington's Disease

Substantial epidemiological studies have established a link between environmental factors and prevalence of neurodegenerative diseases. Increasingly, some studies report a direct cause-and-effect relation between environmental agents such as heavy metals and pesticides, and some neurodegenerative disorders including multiple sclerosis (MS) and Huntington's disease (HD). Interestingly, high blood level of heavy metals and pesticides has been shown in patients with MS and HD. Those agents could be involved directly or indirectly in the pathogenesis of MS and HD. The underlying mechanisms may imply an immune breaking of self-tolerance or neurodegeneration onset of several neurotransmission systems. The chapter will discuss the role of different metals and pesticides in the onset and progress of MS and HD with an overview of the possible underlying pathomechanisms.

Immunological effects of comas in the brain and the impact to healthcare systems

Immunological effects occur in the brain during the duration of a coma. The purpose of this review is to provide information about immunological effects and how they effect a brain experiencing a medically induced coma. Using Galileo and the ProQuest database, information was gathered to project the concepts of how different immunological diseases are affected while being placed in a coma. Coma results from diminished metabolic action in the cerebrum, which might be brought on by brain damage; oxygen deprivation, such as a person having a stroke; or a metabolic disorder. Among the circumstances that can affect metabolic disorder many people recover, while others develop “respirator brain”, some are diabetic, have a high blood level, uremia, or conditions with the kidneys. Coma, related to medicine, is defined as a state of unconsciousness where the patient is unresponsive and is alive but unable to move or react to their surroundings. Comas occur from fatalities, fundamental ailments, injuries, and cerebrum damage. The assumption and administration of the patient who is experiencing a coma requires requests through clinical evaluation that incorporates a careful way to deal with history-taking and systemic and neurological examination. Following revival and intense administration, the level of awareness must be assessed and evidence of meningism, brainstem or lateralizing neurological signs looked for. The prognosis relies upon the basic cause and suitability of intense administration. The diagnosis of cerebrum death depends on upon setting up the aetiology of irreversible brain harm, without reversible causes and building up the absence of any brainstem reflexes.

Pseudo-Bartter’s syndrome in patients with cystic fibrosis: A case series and review of the literature

Introduction. Pseudo-Bartter syndrome (PBS) is characterized by hyponatremic, hypochloremic metabolic alkalosis that mimics Bartter syndrome but with no pathology in the renal tubules. We present five patients with cystic fibrosis (CF) and PBS. Cases Outline. Four children aged between three and five-and-one-half months with previously diagnosed CF and one aged 17 months with previously undiagnosed disease, were hospitalized during the summer season, with severe dehydration, oliguria, apathy and adynamia. Additionally, one of them had an ileostomy due to meconium ileus after birth. All children were on a diet without additional salt intake. Laboratory analysis on admission showed hyponatremia (115-133 mmol/L, mean 122.4 mmol/L), high plasma renin activity (229-500 pg/ml, mean 324 pg/ml) and metabolic alkalosis (pH 7.5-7.6, mean 7.56) in all the patients, and in four of them high blood level of aldosterone (74-560 pg/ml, mean 295.9 pg/ml), hypokalemia (2.3-2.8 mmol/L, mean 2.6 mmol/L), hypochloremia (59-71 mmol/L, mean 66 mmol/L) and low urinary sodium (5-12 mmol/L, mean 9 mmol/L). After intravenous rehydration followed by additional use of sodium and chloride in mean dosis of 1.78 mmol/kg per day, all the patients made a complete recovery. With advice for additional use of salt in the mentioned amount, the patients were discharged from the hospital. Conclusion. PBS is one of CF complications, especially in infants and young children in situations accompanied by increased sweating and/or other causes of additional loss of sodium and chlorine. Sometimes, as was the case with one of our patients, PBS may be the initial presentation form of the disease.

The relevance of serum levels of long chain omega-3 polyunsaturated fatty acids and prostate cancer risk: A Meta-analysis

Objective: Our objective was to systematically analyze the evidence for an association between serum level long chain omega-3 polyunsaturated fatty acid (n-3 PUFA) and prostate cancer risk from human epidemiological studies.Study Procedures: We searched biomedical literature databases up to November 2011 and included epidemiological studies with description of long chain n-3 PUFA and incidence of prostate cancer in humans. Critical appraisal was done by two independent reviewers. Data were pooled using the general variance-based method with random-effects model; effect estimates were expressed as risk ratio with 95% confidence interval (CI). Heterogeneity was assessed by Chi2 and quantified by I2, publication bias was also determined.Results: In total, 12 studies were included. Significant negative association was noted between high serum level of n-3 PUFA docosapentaenoicacid (DPA) and total prostate cancer risk (RR:0.756;95% CI 0.599, 0.955; p = 0.019). Likewise, a positive association between high blood level of fish oil contents, eicosapentaenoicacid (EPA) and docosahexaenoic acid (DHA), and high-grade prostate tumour incidence (RR:1.381; 95% CI 1.050, 1.817; p = 0.021) was noted; however, this finding was evident only after adjustment was done on interstudy variability through the removal of a lower quality study from the pool.Conclusions: High serum levels of long chain n-3 PUFA DPA is associated with reduced total prostate cancer risk. While high blood level of EPA and DHA is possibly associated with increased high-grade prostate tumour risk.

Blood Level Omega-3 Fatty Acids as Risk Determinant Molecular Biomarker for Prostate Cancer

Previous researches involving dietary methods have shown conflicting findings. Authors sought to assess the association of prostate cancer risk with blood levels of omega-3 polyunsaturated fatty acids (n-3 PUFA) through a meta-analysis of human epidemiological studies in available online databases (July, 2012). After critical appraisal by two independent reviewers, Newcastle-Ottawa Quality Assessment Scale (NOQAS) was used to grade the studies. Six case control and six nested case control studies were included. Results showed nonsignificant association of overall effect estimates with total or advanced prostate cancer or high-grade tumor. High blood level of alpha-linolenic acid (ALA) had nonsignificant positive association with total prostate cancer risk. High blood level of docosapentaenoic acid (DPA) had significant negative association with total prostate cancer risk. Specific n-3 PUFA in fish oil, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) had positive association with high-grade prostate tumor risk only after adjustment of interstudy variability. There is evidence that high blood level of DPA that is linked with reduced total prostate cancer risk and elevated blood levels of fish oils, EPA, and DHA is associated with high-grade prostate tumor, but careful interpretation is needed due to intricate details involved in prostate carcinogenesis and N-3 PUFA metabolism.

Combination Therapy of Interferon Beta-1b and Tacrolimus: A Pilot Safety Study

Tacrolimus is a calcineurin inhibitor which works to induce immune suppression by preventing cytokine transcription and lymphocyte activation. Combining the immunomodulator interferon beta-1b (Betaseron) with the immunosuppressant tacrolimus (Prograf) may have the potential of additive therapeutic benefit through the complementary mechanisms of action of these two therapeutics. In this randomized, open-label, multicenter, two-arm pilot study, the authors examined the safety and tolerability of the combination of interferon beta-1b and tacrolimus in relapsing remitting (RRMS) and secondary progressive (SPMS) multiple sclerosis patients who have failed one or more immunomodulatory therapies. Patients (n=25) received a combination of interferon beta-1b subcutaneously every other day and oral tacrolimus (low blood level tacrolimus, 1–5 ng/mL, or high blood level tacrolimus, 5–10 ng/mL) for a period of 38 weeks. The combination therapy of interferon beta-1b and tacrolimus over the 10-month period of the study was shown to be safe and relatively well tolerated. There were no unexpected adverse events occurring as the result of the combination therapy. Further study of this combination therapy in patients with multiple sclerosis unresponsive to conventional therapy is warranted.