Inherited ocular disorders, ophthalmic procedures and carnitines.

L-carnitine plays a role in physiological reactions throughout the body, including sugar aerobic metabolism, oxidative phosphorylation and, most importantly, fatty acid oxidation. In addition, L-carnitine has antiapoptotic, antioxidative and osmolytic properties, which may be useful in the treatment of ocular pathologies (e.g. retinitis pigmentosa [RP] and keratoconus), in corneal tissue repair and in ophthalmic procedures (e.g. photorefractive keratectomy and laser-assisted subepithelial keratectomy [LASEK]). Preliminary studies have suggested that L-carnitine supplementation may be useful in patients with RP. Although studies are warranted to ascertain the benefit of L-carnitine in the LASEK procedure, potentially it could be used instead of alcohol to facilitate epithelial detachment and as a hypo-osmotic solution in the fluid filler used in therapeutic photoablation. Furthermore, its antiapoptotic properties may improve cellular migration, proliferation and adhesion of keratocytes, epithelial cells and endothelial cells, which may be useful in the corneal repair process. Similarly, L-carnitine in high concentrations may prove useful in cross-linking parasurgical treatment of keratoconus, owing to its osmolytic and non-cytotoxic properties

The aging eye and the role of L-carnitine and its derivatives.

The majority of ocular pathologies originate from a functional deterioration of intraocular tissues. This age-related deterioration often occurs as a result of changes within the eye. There is growing interest in the role of natural or synthetic compounds, such as carnitine, for blocking, or slowing, the progress of this deterioration. L-carnitine and its derivatives are involved in numerous physiological reactions, including sugar aerobic metabolism, oxidative phosphorylation, fatty acid oxidation and osmosis. While carnitine levels in human ocular tissue are unknown, animal studies indicate that carnitine is differentially distributed within the eye with the highest concentrations reported in the iris, ciliary body and the choroid-retina. In patients with age-related macular degeneration (AMD), acetyl-L-carnitine improved four parameters of visual function, including visual field mean defect, visual acuity, foveal sensitivity and ocular fundus alterations. L-carnitine has also demonstrated antioxidant properties in animal models of oxidative damage. This article reviews the potential use of L-carnitine and its derivatives in age-related ocular pathologies, such as AMD, cataract, glaucoma and dry eye syndrome

Ocular disorders secondary to systemic disease and the potential role of carnitines.

L-carnitine has a wide-ranging role in several physiological processes, but perhaps most significantly in long-chain fatty acid oxidation in the mitochondrial matrix. Osmolytic (or osmoprotective) properties have also been suggested for the compound. Importantly, the ability of L-carnitine to improve insulin sensitivity in insulin-resistant diabetic patients may, together with the agent's antioxidant and antiapoptotic activity, provide some degree of protection against the progression of diabetic retinopathy. L-carnitine may also protect against the deleterious effects of ocular ischaemic syndrome, and, indeed, acetyl-L-carnitine has been shown to significantly improve retinal damage and visual acuity in patients with monolateral or bilateral retinal artery occlusion. The antioxidant, antiapoptotic and osmolytic properties of L-carnitine also suggest that this agent may have valuable clinical utility in neurotrophic keratopathy and bullous keratopathy. Thus, further detailed investigation of the important clinical potential of L-carnitine in various ocular conditions (e.g. diabetic retinopathy, ocular ischaemic syndrome, neurotrophic keratopathy and bullous keratopathy) that occur secondary to systemic diseases is now clearly warranted

Sarcopenia predicts reduced survival in patients with hepatocellular carcinoma at first diagnosis.

Abstract: Background. Sarcopenia is a complication and independent risk factor for mortality in patients with liver cirrhosis. Aim. To assess the prevalence and influence of sarcopenia on overall survival in a cohort of cirrhotic patients with hepatocellular carcinoma managed in a tertiary center. Material and methods. Abdominal computed tomography of 92 consecutive hepatocellular carcinoma cirrhotic patients, enrolled and followed from 2004 to 2014, were retrospectively studied with a software analyzing the cross-sectional areas of muscles at third lumbar vertebra level. Data was normalized for height, skeletal muscle index (SMI) calculated and presence of Sarcopenia measured. Sarcopenia was defined by SMI ≤ 41 cm2/m2 for women and ≤ 53 cm2/m2 for men with body mass index (BMI) ≥ 25, and ≤ 43 cm2/m2 for men and women with BMI < 25, respectively. Results. Median age at diagnosis was 71.9 years (30.7-86.4) and BMI 24.7 (17.5-36.7), comparable in women 23.1, (17.5-36.7) and men 24.7 (18.4-36.7). A class of CHILD score and BCLC A prevailed (55.4% and 41.3%, respectively); metastatic disease was found in 12% of cases. Sarcopenia was present in 40.2% of cases, mostly in females (62.9%; p = 0.005). Mean overall survival was reduced in sarcopenic patients, 66 (95% CI 47 to 84) vs. 123 (95% CI 98 to 150) weeks (p = 0.001). At multivariate analysis, sarcopenia was a predictor of reduced overall survival, independent of age (p = 0.0027). Conclusions. This retrospective study shows high prevalence of sarcopenia among cirrhotic patients with hepatocellular carcinoma. Presence of sarcopenia was identified as independent predictor of reduced overall survival. As easily measurable by CT, sarcopenia should be determined for prognostic purposes in this patient population

Sequence-Based Identification of Aerobic Actinomycetes

We investigated the utility of 500-bp 16S rRNA gene sequencing for identifying clinically significant species of aerobic actinomycetes. A total of 28 reference strains and 71 clinical isolates that included members of the genera Streptomyces, Gordonia, and Tsukamurella and 10 taxa of Nocardia were studied. Methods of nonsequencing analyses included growth and biochemical analysis, PCR-restriction enzyme analysis of the 439-bp Telenti fragment of the 65 hsp gene, susceptibility testing, and, for selected isolates, high-performance liquid chromatography. Many of the isolates were included in prior taxonomic studies. Sequencing of Nocardia species revealed that members of the group were generally most closely related to the American Type Culture Collection (ATCC) type strains. However, the sequences of Nocardia transvalensis, N. otitidiscaviarum, and N. nova isolates were highly variable; and it is likely that each of these species contains multiple species. We propose that these three species be designated complexes until they are more taxonomically defined. The sequences of several taxa did not match any recognized species. Among other aerobic actinomycetes, each group most closely resembled the associated reference strain, but with some divergence. The study demonstrates the ability of partial 16S rRNA gene sequencing to identify members of the aerobic actinomycetes, but the study also shows that a high degree of sequence divergence exists within many species and that many taxa within the Nocardia spp. are unnamed at present. A major unresolved issue is the type strain of N. asteroides, as the present one (ATCC 19247), chosen before the availability of molecular analysis, does not represent any of the common taxa associated with clinical nocardiosis