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Biomedical subjects

P I Folb

Publications and source records attributed to P I Folb.

At least 19 recordsLinked to original sources
PubMed1996

Erythropoiesis and erythropoietin synthesis during aseptic acute inflammation.

Erythropoietin (Epo) production during acute inflammation induced by s. c. turpentine administration in experimental Long-Evans rats increased in response to reduced erythropoiesis. A close correlation was found between decreased haematocrit (Hct) and increased levels of tumour necrosis factor-alpha (TNF alpha) in this experimental system. The Epo response was not different between rats with acute inflammation and anaemia and control animals with a comparable degree of anaemia. It is concluded that Epo is not an acute phase reactant, and that the Epo response in acute experimental inflammation in rats is explained by the associated development of anaemia.

Acute Disease↗
PubMed1996

Cytokine-mediated inhibition of erythropoietin synthesis by dexamethasone.

The effect of inflammatory cytokines on the in-vitro synthesis of erythropoietin by HepG2 cells was evaluated. Monocyte-conditioned medium, and the cytokines interleukin-1 beta, interleukin-6 and tumour necrosis factor-alpha all reduced synthesis of erythropoietin. The steroidal anti-inflammatory drug, dexamethasone, did not affect cytokine-mediated erythropoietin inhibition. Dexamethasone did cause a reduction in the secretion of erythropoietin inhibitory cytokines from monocytes. These results point to a possible therapeutic approach in the treatment of anaemia caused by suppression of erythropoietin synthesis by monocytic cytokines.

Anti-Inflammatory Agents↗
PubMed1995

Blunted erythropoietin response to anaemia in tuberculosis.

The precise cause of the anaemia that is commonly associated with severe pulmonary tuberculosis (PTB) has not been elucidated. The role of erythropoietin (Epo), the central hormone regulating red cell formation, still awaits clarification. We therefore determined serum Epo levels in patients with PTB; group 1, haemoglobin less than 110 g/L, group 2, haemoglobin greater than 110 g/L; group 3, controls, consisted of matched individuals with uncomplicated iron deficiency; group 4, healthy volunteers. Peripheral blood monocytes were obtained from patients with PTB and the controls, cultured, and the supernatant fluid (SNF) harvested. Tumour necrosis factor alpha (TNF alpha) levels were determined in the SNF, which were then added in various dilutions to a hepatocellular carcinoma cell line (HepG2) capable of regulated EPO synthesis in vitro. The influence of this cytokine was defined by the addition of specific neutralising anti-TNF alpha antibodies in this assay system. Patients in group 1 had significantly lower Epo levels (54 + 11 mU/mL) compared with those in group 3 (142 +/- 41 mU/mL) (p < 0.01). Monocyte supernatants from patients in the anaemic PTB group had markedly elevated TNF alpha levels and significantly suppressed Epo output by HepG2 cells in vitro (p < 0.01). This inhibition was consistently abrogated by anti-TNF alpha antibodies. Serum Epo levels were inappropriately low in untreated PTB patients when compared with corresponding haemoglobin levels in iron deficient controls. This blunted response could be ascribed to release of TNF alpha or other cytokines by activated monocytes.

Anemia↗
PubMed1995

Oxidative stress during antituberculous therapy in young and elderly patients.

Using allantoin (ATN) as a marker for reactive oxygen species (ROS), oxidative stress during antituberculous (anti-TB) therapy was compared in 10 young and 9 elderly patients. Before treatment, ATN plasma concentrations in patients were similar to that of volunteers. Administration of a combination of isoniazid (INH), rifampicin (RIF) and pyrazinamide (PZA) increased plasma ATN in both groups of patients. ATN concentrations (M +/- SE) at six hours were higher (P < 0.05) in elderly than in young patients on day one, 8.22 +/- 1.50 vs 1.89 +/- 0.98 microgram/mL); day 30, (5.85 +/- 0.82 vs 0.87 +/- 0.57 microgram/mL; and day 90, (4.84 +/- 1.24 vs 0.52 +/- 0.50 microgram/mL). Because total amount of ATN excreted was similar in both groups on the three occasions, more ATN was formed in elderly than young patients. In conclusion, there was more oxidative stress in elderly than young patients. It is thereby suggested that Anti-TB drugs induce formation of ROS and elderly patients are at a greater risk of toxicity probably because of poor antioxidant mechanisms.

Adult↗
PubMed1994

Comprehensive assay for pyrazinamide, rifampicin and isoniazid with its hydrazine metabolites in human plasma by column liquid chromatography.

A comprehensive assay for determination of pyrazinamide (PZA), rifampicin (RIF), isoniazid (INH) and hydrazine metabolites is described. The method involves organic solvent extraction of PZA and RIF, followed by derivatization of INH, monoacetylhydrazine (mHYD) and hydrazine (HYD) with salicylaldehyde and extraction with diethyl ether. Acetylisoniazid (acINH) and diacetylhydrazine (dHYD) were hydrolyzed to INH and mHYD, respectively, and processed as above. Using a gradient solvent programmer, PZA and RIF were analyzed on a C8 (5 microns) column at 248 nm, while INH and metabolites were analyzed on a C18 (5 microns) ODS2 column at 280 nm.

Chromatography, High Pressure Liquid↗
PubMed1991

The registration and control of medicines in South Africa: legal issues.

In the provision of health care medicines occupy a central position, both at primary and more advanced levels. Sound medicines have the capability to control and prevent common diseases, and to alleviate suffering. People's confidence in the health services that are provided by the state and by the private sector (as the case may be) is influenced by their knowledge that the medicines that they receive are of good quality and proven efficacy and safety, and that they are continuously available at reasonable cost. A sound national policy for the provision of safe and cost-effective medicines needs to be based on several elements. The most important are: A sound pharmaceutical industry that is able to function in an atmosphere of confidence, with the knowledge that its efforts in support of the public health are understood and respected; and a drug regulatory authority that is trusted for its expertise, independence and integrity. This is as true for a country such as South Africa as it is for a fully industrialised country such as the United States. The regulation and control of medicines in South Africa falls under the aegis of the Medicines Control Council, a statutory body established in accordance with the Medicines and Related Substances Act. In terms of the Act, the council has the mandate to ensure that the medicines available to the South African public are safe, effective, and of high quality, and that their availability is in the public interest. In considering this, the council may take into account only the scientific data available.(ABSTRACT TRUNCATED AT 250 WORDS)

Confidentiality↗
PubMed1988

Drug regulation in South Africa.

South Africa has a population of approximately 30 million people. The country has a mixture of advanced industrial and rural economies, but the medicine control system is consistent with similar systems established in the major industrial countries of Western Europe and North America. Because most of South Africa's population lives in conditions more closely akin to the developing world than to the Western nations, it is important to examine whether the country is optimally served by this drug regulation model and to define critically the strengths and limitations of the established system. The conclusions might be relevant for other countries at a comparable stage of development.

Drug Industry↗
PubMed1988

The effects of in vivo administration of teratogenic doses of vitamin A during the preimplantation period in the mouse.

To examine the effects of vitamin A administered during the preimplantation period, pregnant C3H mice were exposed to teratogenic doses of the vitamin 60 h after copulation. Fetuses were examined for gross abnormalities on the 18th day of gestation and viability, cell number, mitotic index, and chromosome structure were assessed in 81-h blastocysts to determine whether embryotoxic effects were apparent in the preimplantation embryo. There was a reduction in the fetal weight of 18-day fetuses treated in this manner with 15,000 and 30,000 IU vitamin A (p less than 0.0003 in each case), and doses of 10,000 IU and greater were associated with a significantly higher incidence of gross abnormalities. Malformations included exophthalmos, anophthalmia, microphthalmia, exencephaly, exomphalos, and limb defects. Administration of 30,000 IU vitamin A resulted in resorption and intrauterine death in 70% of cases. There was no indication that vitamin A adversely affected 81-h blastocyst viability, cell number, mitotic index, and chromosome structure. The findings suggest that the teratogenic effects that were noted later in fetal life were the result of an action on the developing fetus of the vitamin at a stage later than 81-h and are consistent with the relative resistance of the preimplantation embryo to toxic injury. Persistence of vitamin A, either in the mother or the embryo, is the most likely explanation for the later expression of toxic injury, which is characteristic of the effects that are noted as a result of exposure to the teratogen during the period of organogenesis.

Abnormalities, Drug-Induced↗
PubMed1988

Cyclophosphamide effects on fetal mouse cephalic acetylcholinesterase.

Pregnant C3H mice were exposed to a teratogenic dose of cyclophosphamide (CP, 20 mg/kg body weight) on the 10th day after copulation. Embryos or fetuses were examined 2-9 days later for gross abnormalities, weighed, and assayed for cephalic acetylcholinesterase (EC 3.1.1.7, AChE) activity, and haemoglobin content. In embryos examined 2 days after CP administration, fetal weight and brain weight were less than controls, but cephalic AChE was higher (p less than 0.001). The higher cephalic AChE was associated with a higher absorbance for haemoglobin, although at 14 days there was no apparent difference in the cephalic AChE and absorbance for haemoglobin, compared with controls. At 19 days, fetal weight, brain weight and brain AChE activity were less than controls (p less than 0.001 in each case). The raised cephalic AChE activity in 12-day embryos is explained by the presence of blood, which appears to have resorbed by day 14, whereas the reduced brain AChE activity in 19-day fetuses is accounted for by the growth inhibitory effects of the drug.

Acetylcholinesterase↗