On a possible interrelationship among smoking, gastric ulceration and endogenous prostacyclin.

Investigating either in animals or in humans it seems that smoking exerts an unfavourable effect on the gastric mucosa. The target of this action (among others) is the endogenous prostacyclin content. In gastric ulceration there is a tendency toward decreased endogenous prostacyclin activity even in non-smoker patients, the decrease of which is more pronounced in smokers. The results of animal and human investigations draw attention once again to a possible role of smoking in the development and healing of peptic ulcer disease. Therefore it is always useful for sufferers to give up smoking.

Artemisinin and its derivatives: an important new class of antimalarial agents.

Artemisinin and its derivatives are a potent new class of antimalarials, originated from Artemisia annua, L. The clinical efficacy of these drugs is characterized by an almost immediate onset and rapid reduction of parasitaemia. Their efficacy is high in such areas as well where multidrug-resistance is rampant, but in these areas, their combination with other (effective) antimalarials (e.g., mefloquine) is highly recommended. In this short review, the chemical structures, pharmacological properties, and clinical uses of artemisinin drugs are discussed.

Gastric mucosal endogenous prostacyclin levels are different in Brattleboro rats compared with Wistar strain.

Homozygous Brattleboro rats were investigated and compared to normal (physiological) Wistar strain rats regarding their gastric mucosal endogenous prostacyclin (PG-I(2)) level. It seems that the Brattleboro animals have a significantly lower level of this important protective material. Wistar rats having an artificial pituitary stalk lesion (which is the artificial equivalent of homozygous Brattleboro animals) showed no differences in endogenous mucosal prostacyclin level compared to normal Wistar rats. Therefore, we concluded that this hitherto unknown property of the homozygous Brattleboro rats is genetically determined.

Further analysis of prostacyclin's effect on rat gastric mucosal nucleic acid content.

Graded single and multiple oral doses of prostacyclin enhance, in a direct dose-dependent manner, the DNA and RNA content of rat gastric (antral and fundic) mucosa, resulting in a decreased RNA/DNA ratio. This latter phenomenon is a convincing sign of new cell formation. The arithmetical (theory of functions) analysis of the data resulted in equations, defined mathematically, of prostacyclin's dose-dependent effect.

On a possible new intracellular signal-system in rat gastric mucosa.

It is known that cAMP and cGMP, as an "intracellular second messenger system" play a significant role as a signal system, in the mechanism of action of anti-ulcerogenic (cytoprotective) drugs. According to our present, preliminary investigations it seems that during different experimental circumstances the gastric mucosal 3'-5'-cyclic-cytidine-mono-phosphate (cCMP) 3'-5'-cyclic-uridine-monophosphate and (cUMP) levels were changed--similarly to CAMP and cGMP--and these changes might be a possible indicator of a further, most probably secondary, signal- system role.

Antiretroviral therapeutic possibilities for human immunodeficiency virus/acquired immunodeficiency syndrome.

In human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) illness, the reverse transcriptase and protease (PRT) enzymes of HIV are currently the targets of antiretroviral (ARV) therapy. Nucleoside analogues were the first group of ARV drugs that exerted antiviral activity in patients. More recently, PRT inhibitors have provided new approaches in the treatment of HIV infection and AIDS. Impressive clinical results have been obtained with combination therapies of three ARV drugs, including one PRT inhibitor. It is worth mentioning also that apart from these two main drug groups, there are many new compounds under development, including a vaccine(s) against HIV.

The effect of osmolality changes on gastric mucosal endogenous prostacyclin levels in drug-induced experimental ulcer model of rat.

Osmolality changes evoked with intragastric administration of natural honey or mannitol, significantly decreased the gastric ulceration of rats induced by indomethacin. Together with this effect, a parallel increase was detectable in the mucosal level of endogenous prostacyclin. Although many processes may be involved in this phenomenon, the authors explain their data with a stimulating effect on gastric mucosal microcirculation due to osmolality changes.

Ultrastructural study of liver cell damage induced by ricin.

Experiments were carried out on female albino (Wistar) rats to establish ricin's liver damaging effect. In accordance with the data in the literature it seems that: 1. 2 microg/kg i.p. ricin (investigated 24 h later of its administration) has a detectable hepatotoxic effect; i.e. electron density changes of cells and swelling of mitochondria. These findings correspond to the common and first ultrastructural signs of liver cell damage. This result was further strengthened by the fact that serum ALT and AST values were significantly elevated compared to the control value. 2. The next steps of ricin's damaging effect have been detected at 10 microg/kg i.p. dose,--namely: Effect on smooth endoplasmic reticulum: in its place there is a loose, foam-structured unidentified material,--while in the granulated endoplasmic reticulum the number of ribosomes decreased, similarly to the glycogen granules. 3. 200 microg/kg i.p. ricin caused a severe liver-cell damage. The mitochondria showed early degenerative signs,--and both endoplasmic reticulums were further damaged. The most significant feature is the complete lack of ribosomes in the tubular structure of the granulated endoplasmic reticulum. This latter finding enlights the known inhibitory effect of ricin on protein synthesis. The serum enzyme-levels remained in the pathological range. No early sign of enzyme (Cytochrome P450,) induction could be observed.

Can it be worse? On the sub-Saharan HIV/AIDS epidemic at the beginning of the new millennium.

According to the data in the relevant literature, it seems that at the millennium the worldwide HIV/AIDS epidemic shows no decline. In the most heavily affected area of tropical (sub-Saharan) Africa the situation is getting worse. There is a number of factors which are responsible for this situation. Considering the lack of necessary funds, it is evident that the most important task is a vigorous health education.

Effect of prostacyclin on gastric mucosal RNA-content in the rat.

We investigated changes in gastric (antral and fundic) mucosal RNA contents in single-dose and in long-term (10 weeks) treatment of rats with receiving oral graded doses of prostacyclin. Long-term application of prostacyclin evoked no significant changes, while in the single-dose experiments there was a dose-dependent elevation in RNA-content in both parts of the gastric mucosa. The results are interpreted as convincing signs of the gastro-protective effect of prostacyclin.

Cytoprotection and intracellular calcium.

It seems that prostacyclin has an increasing effect on gastric mucosal (antral and fundic) calmodulin level in rats. Using either the calcium channel blocker verapamil or anti-calmodulin drugs (diazepam, trifluoperazine,) the cytoprotective effect of prostacyclin can be inhibited. Therefore, it is probable that calcium ions and calcium-activated calmodulin play a role in the effect of prostacyclin.

A possible molecular basis for the effect of gastric anti-ulcerogenic drugs.

The exact mechanism of action of the anti-ulcerogenic drugs is still under debate. According to the literature, under normal conditions the cAMP:cGMP ratio in the rat gastric mucosa is approximately 8:10. Following prostacyclin administration, this ratio transiently decreases but later shows a strong elevation, indicating profound changes in the intracellular cyclic nucleotide balance. There is evidence that this elevation or 'shift' in the cAMP:cGMP ratio is linked, on a cellular or molecular level, to the anti-ulcerogenic, cytoprotective processes in the stomach. Cimetidine and ranitidine (widely used H2 receptor-blocking drugs) administered at doses that are too low to interfere with gastric acid secretion, cause an elevation in the cAMP:cGMP ratio, an effect that is also observed with other prostaglandin derivatives and anti-ulcerogenic drugs. In this article, Gabor A. Balint discusses these data and how the elevation of the gastric mucosal cAMP:cGMP ratio is a useful molecular marker that could provide insights into the effects of anti-ulcerogenic drugs.

Selected gastrointestinal pathologies in tropical sub-Saharan Africa.

Doctors need to be well informed about differences in the presentation of certain diseases in tropical and temperate climates. In this article the characteristics of some gastrointestinal diseases, as they recur in sub-Saharan Africa, are briefly reviewed. Diseases of the stomach--including ulcertaion and cancer--are uncommon in Africa, although duodenal ulcer is common all over the tropics. In contrast, colorectal cancer is an extremely rare illness in sub-Saharan Africa, while hepatocellular carcinoma is much commoner than in Europe or North America and the very high incidence of this tumour in tropical countries is cause for concern.

Possible role of endogenous prostacyclin in the maintenance of hepatic integrity in rat.

Exogenously administered prostaglandins are reported to be involved in hepatic regeneration, i.e. they hinder liver cell injury and cell-death induced by different toxic noxae. In the pertinent literature no data are available regarding the role of endogenous (tissue) prostaglandins in hepatotoxic processes. In subchronic carbon-tetrachloride intoxication (800 mg/kg twice a week, s.c., for 12 weeks) the endogenous prostacyclin level showed a transient and significant elevation signalling (similarly to the gastrointestinal tract) the process of protective mechanisms. This tenet was further strengthened by the concomitant decrease of serum ALT and AST levels. Continuing the carbon-tetrachloride treatment, finally not only the endogenous prostacyclin synthesising capacity of the liver but the hepatic cells themselves were also destroyed. According to the author's best knowledge these are the first data in the literature which try to enlighten the protective role of endogenous prostacyclin in hepatotoxic processes.

Situation analysis of HIV/AIDS epidemic in sub-Saharan Africa.

At the end of 1997 about twenty one million persons were living with HIV/AIDS in sub-Saharan Africa, representing almost two third of the world's total. Three broadly defined areas, which include countries with severe epidemics and others with epidemics at their intermediate stage, account for almost 90% of all current HIV infections in tropical Africa. According to World Health Organization (WHO), the current data show very high increases in HIV/AIDS incidence as well as serious underreporting of the disease in the last five years. Sub-Saharan Africa has been particularly hard hit by the disease because of a combination of poor social and health education and also because of other endemic sexually transmitted diseases which significantly increase the chance of HIV transmission.

A novel approach to reduce the unwanted gastric side-effects of orally administered non-steroidal anti-inflammatory drugs in rats.

Among experimental circumstances both cysteine and glutathione, given in the same time as indomethacin or piroxicam, are capable to decrease the unwanted gastric side-effects of the non-steroidal anti-inflammatory drugs. Similar effects were encountered with prostacyclin or D-penicillamine therapy as well but additional prostacyclin therapy is expensive and complicated (its biological half-life is too short;) D-penicillamine has numerous other, non gastrointestinal side-effects, therefore these two latter substances seem to be inferior compared to the previously mentioned ones. Therefore we conclude that in the human non-steroidal anti-inflammatory therapy it would be worthwhile to apply those drugs with a small amount of either cysteine or glutathione to decrease their unwanted side-effects. This assumption is strengthened by the fact that neither cysteine nor glutathione is an unnatural material in the body.

Diagnosis of HIV infection.

AIDS is the clinical manifestation of cellular immunodeficiency caused by HIV infection. A characteristic feature of HIV-infection is the lifelong coexistence of HIV and antibodies against it in the blood. The routine diagnosis of HIV-positivity is based mainly on HIV-antibody screening by ELISA and confirmation by Western blotting. Improvements in diagnostic sensitivity are expected from the introduction of HIV-genome detection by polymerase chain reaction technique.

The effect of different prostaglandins on rat gastric mucosa. Scanning electronmicroscopic investigations.

According to the present investigations prostaglandins showed a specific morphologic effect on (rat) gastric mucosa. Namely: During their effect the foveolae of the mucosa have opened; - which is a convincing sign of mucus production. This phenomenon (i.e. the foveola-opening), showed a direct correlation with the cytoprotective (anti-ulcerogenic) effect of the investigated prostaglandins in the order of PG-I2 > PG-E1 > PG-F2 alpha > 6-keto-PG-F1 alpha.