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Biomedical subjects

M Manku

Publications and source records attributed to M Manku.

8 recordsLinked to original sources

Ethyl-EPA in Huntington disease: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Preliminary evidence suggests beneficial effects of pure ethyl-eicosapentaenoate (ethyl-EPA) in Huntington disease (HD). METHODS: A total of 135 patients with HD were randomized to enter a multicenter, double-blind, placebo-controlled trial on the efficacy of 2 g/d ethyl-EPA vs placebo. The Unified Huntington's Disease Rating Scale (UHDRS) was used for assessment. The primary end point was outcome at 12 months on the Total Motor Score 4 subscale (TMS-4). Analysis of covariance (ANCOVA) and a chi2 test on response, defined as absence of increase in the TMS-4, were performed. RESULTS: A total of 121 patients completed 12 months, and 83 did so without protocol violations (PP cohort). Intent-to-treat (ITT) analysis revealed no significant difference between ethyl-EPA and placebo for TMS-4. In the PP cohort, ethyl-EPA proved better than placebo on the chi2 test on TMS-4 (p < 0.05), but missed significance on ANCOVA (p = 0.06). Secondary end points (ITT cohort) showed no benefit of ethyl-EPA but a significantly worse outcome in the behavioral severity and frequency compared with placebo. Exploring moderators of the efficacy of ethyl-EPA on TMS-4 showed a significant interaction between treatment and a factor defining patients with high vs low CAG repeats. Reported adverse events were distributed equally between treatment arms. CONCLUSIONS: Ethyl-eicosapentaenoate (ethyl-EPA) (purity > 95%) had no benefit in the intent-to-treat cohort of patients with Huntington disease, but exploratory analysis revealed that a significantly higher number of patients in the per protocol cohort, treated with ethyl-EPA, showed stable or improved motor function. Further studies of the potential efficacy of ethyl-EPA are warranted.

Adult↗

Quantification of n-alkanes in stratum corneum in the hereditary ichthyoses.

Chromatographic assay of n-alkanes in skin showed detectable levels in normal controls and in patients with various forms of hereditary ichthyosis. Raised n-alkanes were found in some, but not all, patients with non-bullous and bullous ichthyosiform erythroderma and in individual patients with lamellar ichthyosis, ichthyosis vulgaris and Netherton's syndrome. The finding of elevated scale n-alkanes is neither consistent in ichthyosis, nor specific to any one type of ichthyosis, and n-alkane assay is not helpful in distinguishing one type of hereditary ichthyosis from another. The source of n-alkanes in ichthyotic scale and their role, if any, in the pathogenesis of ichthyosis remain obscure.

Adolescent↗

Essential-fatty-acid metabolites in plasma phospholipids in patients with ichthyosis vulgaris, acne vulgaris and psoriasis.

The concentration of essential fatty acids (EFAs) and their metabolites in plasma phospholipids were measured by gas chromatography in normal individuals, and in patients with ichthyosis vulgaris, acne vulgaris or psoriasis. In all three patient groups, concentrations of arachidonic acid (20:4 omega 6) and docosapentaenoic acid (22:5 omega 6) were significantly below those in controls, suggesting that these abnormalities may occur in many skin diseases. Concentrations of dihomogammalinolenic acid (20:3 omega 6) were low in ichthyosis, normal in acne and elevated in psoriasis. Thus ichthyosis, acne and psoriasis each had a characteristic pattern of EFA metabolites.

Acne Vulgaris↗

Association between keratoconus and atopy.

Sixty-seven patients with keratoconus were classified according to atopic status. Keratoconus patients with and without atopy did not differ significantly with regard to sex, age of onset, or rate of keratoplasty, but patients with very high IgE levels were more prone to graft rejection. Atopy was less common in patients with unilateral keratoconus, and keratoconus occurred more frequently on the side of the dominant hand. There was a significantly lower frequency of HLA B7 in the keratoconus group than in the controls. No abnormalities of essential fatty acid metabolism were found in keratoconus patients with or without atopy. There was no social class bias in the group. The study included a brother and sister with keratoconus and atopy, and a non-atopic patient whose identical twin did not have keratoconus.

Asthma↗

Essential fatty acid supplementation during early alcohol abstinence.

Interactions between ethanol, prostaglandins, and essential fatty acids (EFA) have led to the hypothesis that acute alcohol withdrawal and the sequelae of chronic alcoholism may be related to an EFA/prostaglandin deficiency. To test this hypothesis, EFA profiles in blood-lipid fractions, serum liver enzymes, cognitive function, and alcohol craving were measured in 27 acutely abstinent alcoholics before and after a 3-week double-blind trial of EFA supplementation. Upon entry into the study, alcoholics had significant differences in EFA levels as compared to normal controls, and serum levels of liver enzymes tended to correlate with these EFA levels. After 21 days, cognitive function, alcohol craving, and liver enzymes all improved in both the EFA and placebo groups; most EFA levels also approached normal values. There were no treatment effects of EFA supplementation at the dose used.

Adult↗

Clinical characteristics and serum essential fatty acid levels in hyperactive children.

This study compared 48 hyperactive children with 49 age-and-sex-matched controls. Significantly more hyperactive children had auditory, visual, language, reading, and learning difficulties, and the birth weight of hyperactive children was significantly lower than that of controls (3,058 and 3,410 g, respectively; p less than 0.01). In addition, significantly more hyperactive children had frequent coughs and colds, polydypsia, polyuria, and a serious illness or accident in the past year than controls, but there was no increase in asthma, eczema, or other allergies. Serum essential fatty acid (EFA) levels were measured in 44 hyperactive subjects and 45 controls. The levels of docasahexaenoic, dihomogammalinolenic, and arachidonic acids were significantly lower in hyperactive children than controls (docosahexaenoic: 41.6 and 49.5 micrograms/ml serum respectively, p = 0.045; dihomogammolinolenic: 34.9 and 41.3 micrograms/ml serum, p = 0.007; arachidonic: 127.1 and 147.0 micrograms/ml serum, p = 0.027). These findings have possible therapeutic and diagnostic implications, but further research is needed to attempt to replicate these differences.

8,11,14-Eicosatrienoic Acid↗

Lipid peroxidation in human breast cancer cells in response to gamma-linolenic acid and iron.

Lipid peroxidation in human breast cancer (ZR-75-1) cells and cancer cell killing were confirmed by using ultraviolet (UV)-spectrophotometry and mass spectrometry (MS). ZR-75-1 cells and human normal fibroblast CCD-41-SK (41Sk) cells were cultured with gamma-linolenic acid (GLA) and ferrous iron Fe (II) combinations. Formation of lipid peroxide and cytotoxic effect were highest in ZR-75-1 cells treated with GLA + Fe (II), though 41Sk cells showed little evidence of either lipid peroxidation or cytotoxity. These results indicate a cancer-cell-specific lipid peroxidation mechanism in association with the selective cancer cell killing effect in response to GLA.

Antineoplastic Agents↗