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Distal symmetric polyneuropathy (DSP) is the most common variety of neuropathy. Since the evaluation of this disorder is not standardized, the available literature was reviewed to provide evidence-based guidelines regarding the role of autonomic testing, nerve biopsy, and skin biopsy for the assessment of polyneuropathy.

Distal symmetric polyneuropathy (DSP) is the most common variety of neuropathy. Since the evaluation of this disorder is not standardized, the available literature was reviewed to provide evidence-based guidelines regarding the role of laboratory and genetic tests for the assessment of DSP.

Hereditary motor-sensory neuropathy or the Charcot-Marie-Tooth syndrome is known to represent considerable genetic heterogeneity. Onset is usually in childhood, adolescence, or young adulthood. The objective of this study was to define late-onset forms of the disorder.

The objective of this report was to develop a case definition of distal symmetric polyneuropathy to standardize and facilitate clinical research and epidemiologic studies. A formalized consensus process was employed to reach agreement after a systematic review and classification of evidence from the literature. The literature indicates that symptoms alone have relatively poor diagnostic accuracy in predicting the presence of polyneuropathy; signs are better predictors of polyneuropathy than symptoms; and single abnormalities on examination are less sensitive than multiple abnormalities in predicting the presence of polyneuropathy. The combination of neuropathic symptoms, signs, and electrodiagnostic findings provides the most accurate diagnosis of distal symmetric polyneuropathy. A set of case definitions was rank ordered by likelihood of disease. The highest likelihood of polyneuropathy (useful for clinical trials) occurs with a combination of multiple symptoms, multiple signs, and abnormal electrodiagnostic studies. A modest likelihood of polyneuropathy (useful for field or epidemiologic studies) occurs with a combination of multiple symptoms and multiple signs when the results of electrodiagnostic studies are not available. A lower likelihood of polyneuropathy occurs when electrodiagnostic studies and signs are discordant. For research purposes, the best approach to defining distal symmetric polyneuropathy is a set of case definitions rank ordered by estimated likelihood of disease. The inclusion of this formalized case definition in clinical and epidemiologic research studies will ensure greater consistency of case selection.

Fungal isolate F01V25 was obtained from the alga Dictyosphaeria versluyii collected near Dravuni, Fiji, in 2001 and represented a previously undescribed Penicillium sp. Fermentation of isolate F01V25 resulted in the production of two new polyketides, dictyosphaeric acids A and B, along with the known anthraquinone carviolin. The relative stereochemistry of dictyosphaeric acids A and B was determined using the J-based configuration analysis method in conjunction with ROE and NOE correlations.

Neutramycins B−G were purified from a historical sample of neutramycin in our antibiotic collection. The structures of the compounds were solved by 2D NMR spectroscopic analysis. Four of the compounds (2−5) are probable biosynthetic intermediates or shunt metabolites of neutramycin biosynthesis, while two (6, 7) are likely to be degradation products. Only one intermediate (5) showed weak Gram-positive activity.

Two novel sulfur-containing analogs of the immunosuppressive natural product rapamycin (1) were obtained by feeding cultures of Streptomyces hygroscopicus with l-nipecotic acid (4) and either (S)-1,3-thiazane-4-carboxylic acid (5) or (S)-1,4-thiazane-3-carboxylic acid (6). The structures of the two new compounds, 20-thiarapamycin (2) and 15-deoxo-19-sulfoxylrapamycin (3), were determined by spectroscopic methods.

The oceans with their diverse life forms cover greater than 70% of the earth's surface and present themselves as an unexplored area of opportunity. Owing to the many habitats in the sea, marine microorganisms encompass a complex and diverse assemblage of microscopic life forms, of which only 1% have been cultured or identified. Although just initiated in the past decade, natural products drug discovery from marine microorganisms has been encouraging. The chemical and biosynthetic diversity of these microbial compounds, coupled with their pharmacological activities, harbors great potential for the discovery of new antibiotics to combat the evolving resistance of pathogens to existing drugs. In this review, we summarize the diverse compounds identified from marine microorganisms and their potential as new antibacterial and antifungal drugs.

Herein we report a significant body of spectroscopic data that supports the originally proposed structure of medermycin/lactoquinomycin A. In addition, we demonstrate that these data are inconsistent with the revised structure reported recently in the literature.

The full structure of ganefromycin α has been determined. The relative configurations were determined from ³JH,H coupling constants and NOE data, while the absolute configurations in moieties A and B were determined separately by difference CD of their acylate derivatives, which showed typical exciton couplets. The configurations of the stereogenic centers in ganefromycin α are 8S, 9S, 11R, 12S, 13S, 21S, 22R, 23R, 24R, and 26S.

The biosynthetic pathway of ganefromycin α (8) was investigated using blocked mutants of Streptomyces lydicus spp. tanzanius, the ganefromycin α producer, in conjunction with bioconversion experiments with the products of these mutants. Compounds 1−7 and 9−15, which are structurally related to ganefromycin α, were produced by cultures of secretor mutants showing blockage or diminished production of 8. These compounds were isolated, characterized, and subjected to bioconversion experiments using converter and other secretor mutants. Some of the compounds were shown to be products resulting from blocks at various stages in the biosynthetic pathway beyond construction of the polyketide skeleton (e.g., furan ring closure, hydroxylation, glycosylation, etc.). Other compounds were not bioconverted by biosynthetically capable mutants and were deemed shunt products. A mutant's metabolites and bioconverting ability were used to surmise the location of the block. A picture of the later sequence of events leading to the synthesis of ganefromycin α emerged, including C23-hydroxylation, C13a-O-methylation, C21a-hydroxylation, and C21a-O-glycosylation. Some of the later steps in the biosynthetic pathway for ganefromycin α are proposed.

To evaluate the acute effects of inorganic lead on oxidative metabolism in hepatocytes, intact liver cells were isolated from hamsters and incubated with solutions of Pbcl2. These cells were found to be relatively resistant to respiratory inhibition as compared to liver homogenates. That is, in the presence of 1 mM PbCl2, the rate of oxygen consumption of the intact cells was approximately 6% less than that of controls. In contrast, the respiratory rates of liver homogenates treated with 1 mM PbCl2 were about 70% lower than controls. The resistance of the intact cells persisted even after 41/2 h of incubation with the lead and appears to reflect the protective influence of the plasma membrane.

Along with dioxapyrrolomycin (1), four new pyrrolomycin antibiotics, namely, pyrrolomycin G (3), pyrrolomycin H (4), pyrrolomycin I (5), and pyrrolomycin J (6), were produced in cultures of Streptomyces fumanus. Apart from dioxapyrrolomycin, pyrrolomycin G and pyrrolomycin H are the only other chiral members of the pyrrolomycin family of antibiotics, and their absolute stereochemistry was deduced to be 13S. Here, we report the isolation, structure elucidation, and antimicrobial activity of these new pyrrolomycins.

The structure of a new dibenzodiazepine alkaloid, diazepinomicin (1), isolated from the culture of a marine actinomycete of the genus Micromonospora was characterized using spectroscopic methods. Diazepinomicin represents a unique molecular class composed of a dibenzodiazepine core linked to a farnesyl side chain.