Organophosphate induced delayed polyneuropathy

This review discusses the current understanding of organophosphate induced delayed polyneuropathy (OPIDP) with emphasis on molecular mechanisms, pathogenesis and possibilities for prevention/therapy. OPIDP is a rare toxicity caused by certain organophosphorus compounds (OP) characterized by degeneration of some long axons in the central and peripheral nervous system that appear about 2-3 weeks after exposure. The molecular target for OPIDP is considered to be an enzyme in the nervous system known as neuropathy target esterase (NTE). NTE can be inhibited by two types of inhibitors: a) phosphates, phosphonates, and phosphoramidates, which cause OPIDP when >70% of the enzyme is inhibited, and b) phosphinates, carbamates, and sulfonyl halides which inhibit NTE and cause either protection from, or promotion, of OPIDP when given before or after a neuropathic OP, respectively. The ability of a NTE inhibitor to cause OPIDP, besides its affinity for the enzyme, is related to its chemical structure and the residue left attached to the NTE. If such residues undergo the aging reaction i.e. the loss of an alkyl group bound to the enzyme, those OPs usually have a high likelihood of causing OPIDP. Protection from neuropathic doses of OP inhibitors is obtained when NTE is inhibited with nonageable inhibitors. Promotion of OPIDP involves another site besides NTE because it can occur when all NTE is affected. It is now known that this other site is similar to NTE in that it is also sensitive to mipafox but at much higher concentrations. Promotion affects either the progression or expression of OPIDP after the initial biochemical effect on NTE. Some recent observations suggest that development of OPIDP in hens can be influenced by atropine, oximes and methylprednisolone when they are given before or soon after neuropathic OPs.     

Anal condyloma and HIV-associated anal disease

Although there are a large variety of anal diagnoses associated with the HIV population, anal condyloma and anal ulcerations make up the vast majority. A large percentage of individuals having multiple concurrent pathologies should also be noted. Thus, this article concentrates on anal condyloma, anal ulceration and HIV, making note of other significant issues.     

Benzodiazepines enhance the bicuculline-sensitive part of recurrent Renshaw inhibition in the cat spinal cord

The effects of intravenous diazepam and midazolam on recurrent Renshaw inhibition of lumbar motoneurones were studied in unanaesthetized spinal cats. Both benzodiazepines enhanced the bicuculline-sensitive, late part of recurrent inhibition without affecting its strychnine-sensitive, early component. The results support the view that some Renshaw cells are GABAergic and extend the potentiating effect of benzodiazepines to a spinal GABAergic synapse that mediates postsynaptic inhibition.     

Viral hepatitis: Croatian consensus statement

There has been a dramatic improvement in diagnostic procedures and therapy of viral hepatitis in the last 20 years. Improvements in therapy caused an increase in actual cost, however, with significant long-term savings through a decreased cost of treatment of advanced liver disease including liver transplantation. The Croatian National Board for Viral Hepatitis has decided to initiate the organization of consensus conference on viral hepatitis enabling the leading experts in the country to give the best possible recommendations for the diagnosis, prophylaxis and therapy in our circumstances. The Consensus Conference took place in Zagreb in June 2004, with update in March 2005, organized by the Croatian National Board for Viral Hepatitis, Reference Centers of the Ministry of Health for Chronic Liver Diseases, Infectious Diseases and AIDS, Croatian Society of Gastroenterology--Hepatology Section, Croatian Society for Nephrology, Dialysis and Transplantation, and Croatian Institute for Health Insurance. Invited experts provided written reports on the respective subjects that appear in this issue and their recommendations resulting in this consensus statement.     

Sequence requirements for oligodeoxyribonucleotide inhibitory activity

Inhibitory oligonucleotides (IN-ODN) differing from stimulatory CpG ODN (ST-ODN) by as few as two bases can block ST-ODN-induced proliferation, apoptosis protection and IL-6 secretion in B lymphocytes and the production of IL-12p40 by non-B cells. The main objective of this study was to determine the ODN sequence requirements for inhibition in mice. Starting with a strongly inhibitory 15-mer prototype phosphorothioate sequence, we tested the 60 sequences that differed from the prototype by one base, revealing the three areas that are critical for activity. Between these areas were the spacer sequences where base composition mattered little, but the number of bases was important. Truncation of three bases at the 3' end of the 15-mer and one at the 5' end was tolerated with minimal loss of activity. This approach yielded an 'optimal' sequence of 5' CC x notC notC xxGGGx or CC x notC notC xGGGxx 3', where x is any base. The sequence requirements for optimal inhibition of B cell responses to Type B (K) ODN and mixed splenocyte IL-12p40 responses to Type A (D) ODN were strikingly similar. Inhibition of ST-ODN by IN-ODN was competitive. A hypothetical model of the ODN-binding site is proposed. Synthetic IN-ODN with the sequence characteristics defined here should provide antidotes for excessive innate reactions to DNA.     

The aqueous humour antioxidative capacity in different types and color of the age-related cataract

BACKGROUND/AIM: Oxidative stress results from increased oxidative processes, decreased antioxidative protection, or both processes simultaneously. Photooxidative stress, as a form of oxidative stress, induced by the energy of solar radiation, today is considered as crucial in the age-related cataractogenesis. Other known and unknown, endogenous and egsogenous factors that contribute to the oxidative stress intensity, can influnce the cataract type and brunescence. Thus the oxidative stress intensity and its form might determine the cataract type and brunescence, and also make the efforts in cataract prevention more complex. Hence, the objective of the present paper was to investigate the current amount of antioxidative capacity in aqueous humour during the cataract genesis of different types and pigmentation of cataract. METHODS: Transversal review of 80 samples of humour aqueous obtained during extracapsular cataract extraction. Aqueouses were analyzed by tiobarbituric acid (TBA) method for the total antioxidant activity estimation, expressed as %iMDA, and by using 0.1 ml of aqueous. RESULTS: The mixed type of cataract showed the statistically significantly lower values of the intensities of antioxidative protection in aqueous humour compared to cortical and nuclear cataracts (p < 0.001, respectively). Between pure nuclear and cortical cataracts we found the small differences of the investigated parameter, but they pointed to the decreased level of antioxidative protection, i.e. the increased intensity of the aqueous humour oxidative stress in the cortical cataract type. A significant correlation betweer the cortical cataract maturation and the %iMDA (p < 0.05) was found. CONCLUSIONS: The role of the oxidative stress, here expressed as the antioxidative capacity of aqueous humour, could not be the same for all the cataract types. The lower level of antioxidative protection of aqueous in brunescent and mixed cataracts may point to the higher intensity of oxidative stress in those cataract types. The correlation betweer the cortical cataract maturity and %iMDA points to the significant decrease of the aqueous antioxidative protection in the cataract progression.