Synthesis and biological activities of d-chiro-inositol analogues with insulin-like actions.

d-chiro-inositol (DCI, 1) evokes therapeutic actions in diabetes and insulin resistance but has sub-optimal pharmacokinetic profiles. To investigate what positions on the DCI cyclohexanol ring may be amenable to modification to improve pharmaceutical formulations, a series of analogues based on DCI were synthesised. These compounds were then evaluated for their ability to stimulate glucose transport using 3T3-L1 adipocytes as a model system. Positional analyses indicate that the hydroxyl group at position 1 is not essential for activity and can be modified without affecting glucose uptake. Removal of the hydroxyl at position 3 also had minimal effect on activity but this group is sensitive to modification. By comparison, the oxygen at position 2 is crucial to the potency of DCI, although this group can withstand modification without fundamentally affecting activity. These data reveal that positions 1 and 2 on the cyclohexanol ring of DCI offer further scope for modification to develop DCI analogues with desirable pharmacokinetic profiles for the potential treatment of metabolic disease.

New syntheses of 1D- and 1L-1,2-anhydro-myo-inositol and assessment of their glycosidase inhibitory activities.

The 1D and 1L enantiomers of 1,2-anhydro-myo-inositol (conduritol B epoxide) were synthesised from 1D-pinitol and 1L-quebrachitol, respectively, and their activities were compared in selected glycosidase inhibition assays. The 1D enantiomer was found to be the active isomer, functioning as an irreversible inhibitor of sweet almond beta-D-glucosidase. Neither isomer was active against the alpha-D-glucosidase from Bacillus stearothermophilus or the beta-D-galactosidase from Aspergillus oryzae.

1D-3,4-Di-O-(diphenylmethylphosphonio)-1,2,5, 6-tetra-O-methyl-chiro-inositol diiodide.

The title compound, 3,4,5,6-tetramethoxycyclohexane-1, 2-diyldioxybis(methyldiphenylphosphonium) diiodide, C(36)H(44)O(6)P(2)(2+).2I(-), was prepared from a New Zealand natural product, D-chiro-inositol, in order to develop new catalytic metal complexes. The inositol ring retains its usual chair conformation with only minor perturbations caused by the bound diphenylmethylphosphines. Crystal-packing forces are provided by C-H. I cation-anion interactions.

Estimation of maximum tolerated dose for long-term bioassays from acute lethal dose and structure by QSAR.

A quantitative structure-activity relationship (QSAR) model has been developed to estimate maximum tolerated doses (MTD) from structural features of chemicals and the corresponding oral acute lethal doses (LD50) as determined in male rats. The model is based on a set of 269 diverse chemicals which have been tested under the National Cancer Institute/National Toxicology Program (NCI/NTP) protocols. The rat oral LD50 value was the strongest predictor. Additionally, 22 structural descriptors comprising nine substructural MOLSTAC(c) keys, three molecular connectivity indices, and sigma charges on 10 molecular fragments were identified as endpoint predictors. The model explains 76% of the variance and is significant (F = 35.7) at p less than 0.0001 with a standard error of the estimate of 0.40 in the log (1/mol) units used in Hansch-type equations. Cross-validation showed that the difference between the average deleted residual square (0.179) and the model residual square (0.160) was not significant (t = 0.98).

Cytologic detection of penile malignant melanoma of soft parts in pleural effusion using monoclonal antibody HMB-45.

A case of penile malignant melanoma of soft parts ("clear cell sarcoma") with pulmonary metastases and malignant effusions is reported. The tumor cells in the pleural effusion were scattered singly and admixed with reactive mesothelial cells. They had abundant granular cytoplasm and round nuclei with prominent nucleoli. Although staining for S-100 protein was positive in sections from the penile lesion, it was negative in sections of a cell block prepared from the effusion; however, the effusion tumor cells demonstrated immunoreactivity with HMB-45, an antimelanoma monoclonal antibody.

MR imaging in seminal vesiculitis.

Seminal vesicle disorders may be clinically vague owing to the nonspecific nature of the associated signs and symptoms. Thus, the diagnosis of seminal vesicle disease is frequently difficult. Two cases of seminal vesiculitis are presented to illustrate the usefulness of pelvic magnetic resonance imaging in making this difficult diagnosis.

The surgeon's garb.

A comprehensive evaluation of all factors associated with the surgeon's garb worn with and without laminar air flow revealed that in a conventional operating room, all personnel should wear an impermeable one-piece suit with foot attachments, any type of head cover, and, if they are going to be near the operative site or instrument table, a disposable mask. Scrub personnel should wear some type of a disposable gown to reduce the amount of surface contamination. The best way to reduce the environmental and surface contamination would be for all personnel to wear some type of a hooded exhaust equipment, but this is impractical both for circulating nurses and for anesthesiologists. Despite the reduction obtained from all the above controls, the reduction in the amount of bacterial contamination would not be as great as that obtained with laminar air flow, 93% (p < 0.005). Laminar air flow produced the greatest single reduction in environmental and surface contamination and variables such as time, people and attire did not influence the overall counts. The attire recommended for the conventional operating room can be used in laminar air flow with an expectation of overall reduction in contamination.

Temporal patterns of the use of non-prescribed drugs: some behavioral correlates.

Previous studies of the temporal patterns of the use of non-prescribed psychoactive drugs have been primarily limited to users' self-reports. Two behavioral indicators, times of arrest for driving while intoxicated and times of calls to a drug information service, yield temporal patterns very similar to those obtained from users' reports.

The effect that time, touch and environment have upon bacterial contamination of instruments during surgery.

Hemostats were evaluated for frequency of contamination and such contamination was correlated with increasing operating room exposure time. The studies were performed under surgical conditions in operating rooms with and without laminar air flow. The study was also designed to show whether contamination of hemostats were influenced by the scrub nurse's handling. Hemostats were more frequently contaminated in the conventional operating room without laminar air flow (P less than 0.001). Handling by the scrub nurse's gloved hand statistically increased the number of contaminated hemostats (P less than 0.01). Laminar air flow reduced the frequency of contamination statistically (P less than 0.001) to a point where time and touch by a gloved hand of the scrub nurse were not important factors.

The operating room environment as affected by people and the surgical face mask.

The microbiological counts were determined in an operating room suite of 8 rooms and a hallway. The bacterial counts in an empty operating room jumped statistically from 13 CFU/ft2/hr (+/- 31) to 24.8 (+/- 58.8) when the doors were left open (people in the hallways) and 447.3 (+/- 186.7) when 5 people were introduced. The wearing of a surgical face mask had no effect upon the overall operating room environmental contamination and probably work only to redirect the projectile effect of talking and breathing. People are the major source of environmental contamination in the operating room.

Rodac plate-holding device for sampling surfaces during surgery.

A Rodac plate-holding device has been developed to facilitate microbial surface sampling of supposedly sterile items in the operating room during surgery.