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Biomedical subjects

M M Jones

Publications and source records attributed to M M Jones.

276 records · Page 16Linked to original sources
PubMedDate not supplied

Dithiocarbamates and cadmium metabolism: further correlations of cadmium chelate partition coefficients with pharmacologic activity.

N,N-bis(beta-Hydroxyethyl)dithiocarbamate (DHDC), N-methyl-N-hydroxyethyldithiocarbamate (MHDC), and N-ethyl-N-hydroxyethyldithiocarbamate (EHDC) were compared for their relative efficacies in promoting organ mobilization and excretion of metallothionein-bound cadmium (Cd). An attempt was made to correlate certain aspects of their pharmacodynamic properties with the octanol/aqueous partition coefficient of each Cd-dithiocarbamate complex. All compounds assessed were effective in mobilizing renal, intestinal, and testicular Cd. Those analogs with slightly greater lipid than aqueous solubility were more effective in this regard (DHDC less than MHDC less than EHDC). However, those analogs with higher lipid solubility (log10P greater than 0) promoted redistribution of Cd to liver. Only DHDC, with the lowest lipid solubility (log10P = -0.3 to -0.6), promoted Cd excretion. None of the congeners effected any redistribution of Cd to brain. Methods of preparation of the sodium salts of these analogs are described in detail.

Animals↗
PubMedDate not supplied

Prevention of cisplatin-induced toxicity by selected dithiocarbamates.

Cisplatin (CDDP) is a widely used antineoplastic agent, the administration of which is associated with dose-related toxicities. Currently, ototoxicity is the dose-limiting toxicity of cisplatin and difficult to prevent. The purpose of this study was to determine the ability of two substituted dithiocarbamates, diethyldithiocarbamate (DDTC) and N-methyl-D-glucaminedithiocarbamate (NMGDTC) to abrogate cisplatin-induced toxicity in young female Hartley albino guinea pigs. The animals were divided into saline controls, CDDP only, NMGDTC only, and CDDP-DDTC or CDDP-NMGDTC combinations with DDTC or NMGDTC given 30 minutes before or 30 minutes after CDDP. Auditory brainstem responses (ABR) were recorded periodically in sound-attenuated rooms to assess hearing thresholds. Representative cochleas were harvested at autopsy, processed, and examined by scanning electron microscopy (SEM). The NMGDTC produced marked reduction of CDDP-induced ototoxicity and weight loss. No significant ABR shift was found regardless of the order of CDDP and NMGDTC administration, but the derivative was more effective in preventing anorexia and weight loss when given prior to CDDP. Specifically, groups of guinea pigs given NMGDTC prior to CDDP showed the only weight gain among the treatment groups. Diethyldithiocarbamate, the other dithiocarbamate evaluated in this study, did not provide protection from cisplatin ototoxicity regardless of the order of administration. A CDDP-induced weight loss was reduced when DDTC was administered prior to CDDP. In summary, NMGDTC given prior to CDDP offers remarkable protection against cisplatin-induced ototoxicity and weight loss. It may help eliminate dose-limiting cisplatin-induced toxicity and allow the use of cisplatin at higher doses in cancer chemotherapy.

Animals↗
PubMedDate not supplied

Efficacy of transnasal butorphanol tartrate in postepisiotomy pain: a model to assess analgesia.

Butorphanol tartrate, a synthetically derived opioid agonist-antagonist analgesic, was tested in a large group of postpartum women (N = 76) to assess the safety and analgesic efficacy of a recently approved transnasal preparation of this drug in the relief of postepisiotomy pain. The safety and efficacy of intravenous and intramuscular administration of butorphanol tartrate has been established over 14 years of clinical use. The new nasal spray dosage form offers a similar degree of efficacy with a rapid onset of action. Compared with the injectables and other drugs in this class, transnasal butorphanol has a longer duration of action (4 to 5 hours). In this double-blind, parallel-group, dose-response study, 76 female patients ages 17 to 37 years with moderate to severe postepisiotomy pain were randomly assigned to receive a single dose of transnasal butorphanol (0.25, 0.5, 1, or 2 mg) or placebo. The patients were evaluated for 6 hours. The results of the study indicate that the 1-mg and 2-mg doses were associated with greater efficacy compared with placebo using several markers for efficacy, including the pain relief score and time to remedication. The drug was well tolerated, dizziness and drowsiness being the most frequently reported adverse effects. Adverse effects appeared to be dose related.

Administration, Intranasal↗
PubMedDate not supplied

Inhibitory effects of seven organosulphur compounds on clinical isolates of Candida species in vitro.

Thirty clinical isolates of Candida albicans and 10 other Candida species were tested for susceptibility to 6 substituted dithiocarbamates and one dimercaptosuccinate. Dimethyldithiocarbamate, sodium pyrrolidine dithiocarbamate, and sodium diethyldithiocarbamate showed dose-dependent antifungal activity which was partially reversed by the addition of zinc, copper, or iron sulfate with greatest reversal at 2:1 metal to dithiocarbamate molar ratio. Anaerobiosis also interfered with dithiocarbamate antifungal activity.

Anaerobiosis↗
PubMedDate not supplied

Hereditary hemochromatosis.

Genetic (hereditary) hemochromatosis is probably the most common autosomal recessive disorder found in white Americans, of whom about 5/1,000 (0.5 percent) are homozygous for the associated gene. The hemochromatosis gene is probably located close to the HLA-A locus on the short arm of chromosome 6. Homozygous individuals may develop severe and potentially lethal hemochromatosis, especially after age 39. Hereditary hemochromatosis involves an increased rate of iron absorption from the gut with subsequent progressive storage of iron in soft organs of the body. Excess iron storage eventually produces pituitary, pancreatic, cardiac, and liver dysfunction and death may result from cardiac arrhythmias, congestive heart failure, and/or hepatic failure or cancer. Early diagnosis can prevent these excess iron-induced problems. Iron overload owing to HLA-linked hereditary hemochromatosis can be distinguished from other causes of hemochromatosis by liver biopsies and interpretations. Patients at risk for genetic hemochromatosis should be screened, identified, and treated as early as age 20 to prevent or minimize the deadly complications of hemochromatosis. Population screening should include measurements of serum iron concentration, total iron binding capacity (TIBC), percent saturation of transferrin, and serum ferritin concentrations. Family members of hereditary hemochromatosis patients are at increased risk and should be tested. Screening, identification and early treatment (phlebotomies, sometimes in combination with the use of Desferal or other iron-chelating agents) may help prevent or reduce iron-related organ damage and premature deaths. Early diagnosis and treatment will reduce the population of aging individuals with severe, complicated hemochromatosis and dramatically reduce medical costs (billions of U.S. dollars per annum) associated with the management of this disease.

Adult↗