Synthesis of [13C6]primaquine

In support of a program to identify toxic metabolites of the antimalarial, primaquine, its [¹³C₆] analog was prepared from [¹³C₆] anisole in seven steps.     

Therapeutic potential of targeting the renin angiotensin system in portal hypertension

Portal hypertension is responsible for the bulk of the morbidity and mortality in patients with cirrhosis.Drug therapy to reduce portal pressure involves targeting two vascular beds.The first approach is to reduce intra hepatic vascular tone induced by the activity of powerful vasocontrictors such as angiotensin Ⅱ,endothelin-1 and the sympathetic system and mediated via contraction of perisinusoidal myofibroblasts and pervascular smooth muscle cells.The second approach is to reduce mesenteric and portal blood flow.Non-selective b-blockers are widely used and have been shown to prolong patient survival and reduce oesophageal variceal bleeding in advanced cirrhosis.However many patients are unable to tolerate these drugs and they are ineffective in a significant proportion of patients.Unfortunately there are no other drug therapies that have proven efficacy in the treatment of portal hypertension and prevention of variceal bleeding.This review briefly outlines current therapeutic approaches to themanagement of portal hypertension,and the evidence supporting the role of the renin angiotensin system(RAS) and the use of RAS blockers in this condition.It will also outline recent advances in RAS research that could lead to the development of new treatments focusing in particular on the recently discovered "alternate axis" of the RAS.     

Current therapies and novel approaches for biliary diseases

Chronic liver diseases that inevitably lead to hepatic fibrosis, cirrhosis and/or hepatocellular carcinoma have become a major cause of illness and death worldwide. Among them, cholangiopathies or cholestatic liver diseases comprise a large group of conditions in which injury is primarily focused on the biliary system. These include congenital diseases(such as biliary atresia and cystic fibrosis), acquired diseases(such as primary sclerosing cholangitis and primary biliary cirrhosis), and those that arise from secondary damage to the biliary tree from obstruction, cholangitis or ischaemia. These conditions are associated with a specific pattern of chronic liver injury centered on damaged bile ducts that drive the development of peribiliary fibrosis and, ultimately, biliary cirrhosis and liver failure. For most, there is no established medical therapy and, hence, these diseases remain one of the most important indications for liver transplantation.As a result, there is a major need to develop new therapies that can prevent the development of chronic biliary injury and fibrosis. This mini-review briefly discusses the pathophysiology of liver fibrosis and its progression to cirrhosis.We make a special emphasis on biliary fibrosis and current therapeutic options,such as angiotensin converting enzyme-2(known as ACE2) over-expression in the diseased liver as a novel potential therapy to treat this condition.     

Pesticide resistance mechanisms produced by field selection pressures on Anopheles nigerrimus and A. culicifacies in Sri Lanka

In Sri Lanka, Anopheles nigerrimus is resistant to a range of organophosphate and carbamate insecticides at both the larval and adult stages. Biochemical studies indicate that an alteration in acetylcholinesterase is the basis of resistance rather than increased metabolic breakdown of the insecticides. In contrast, A. culicifacies is resistant only to malathion and closely related compounds containing a carboxylate ester bond. Agricultural pesticides are the sole source of selection pressure for resistance in A. nigerrimus, while in A. culicifacies pressure arises predominantly from antimalarial spraying.     

Testicular secretion of inhibin in the male golden hamster (Mesocricetus auratus)

To identify the cellular source of inhibin in the male golden hamster, we have used complementary approaches, immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). Strong positive staining of the inhibin alpha subunit was observed in both the Sertoli and Leydig cells of the testes. No specific staining was observed for the inhibin betaA subunit, whereas specific staining for the inhibin betaB subunit was strongly positive in the Leydig cells. Inhibin pro-alphaC and inhibin B were detected in peripheral plasma, and testicular homogenate also contained large amounts of inhibin pro-alphaC and inhibin B. However, inhibin A was not detected either in peripheral plasma or in testicular homogenate. Plasma concentrations of inhibin pro-alphaC and inhibin B were significantly (P < .001) decreased 24 hours after orchidectomy. These results strongly suggest that the Leydig cells are the main source of dimeric inhibin B in the male golden hamster.     

Insecticide resistance in Anopheles sacharovi Favre in southern Turkey

We report the resistance to 12 insecticides of specimens of Anopheles sacharovi, both in laboratory cultures and those collected in the malarious areas of Adana, Adiyaman, Antalya, Aydin, and Muğla in southern Turkey. Mortality was higher 24 h after exposure than immediately after exposure but was unaffected by temperature (24 degrees C or 29 degrees C) or the position of the test kit (horizontal or vertical). In Adana, Adiyaman and Antalya, A. sacharovi was susceptible only to malathion and pirimiphos-methyl. In Aydin it was susceptible to both these insecticides as well as to dieldrin, lambda-cyhalothrin, and etofenprox; and in Muğla it was susceptible to dieldrin, fenitrothion, lambda-cyhalothrin, cyfluthrin and etofenprox, as well as to malathion and pirimiphos-methyl.     

Botulinum toxin for treatment of craniofacial hyperhidrosis

The effect of botulinum toxin A (BTX) was studied on 12 patients with idiopathic craniofacial hyperhidrosis. After confirming the diagnosis by Minor's iodine starch test we first treated one-half of the forehead with an injection of 2.5–4 ng BTX (Dysport) equidistantly intracutaneously. After 4 weeks we assessed the efficacy by another Minor's iodine starch test and then treated the other half. Another 4 weeks later a standardized telephone interview was carried out. After 1–7 days the craniofacial sweating in the area injected had completely ceased in 11 patients and was mildly reduced in the remaining one. The efficacy was confirmed by repeated Minor's iodine starch tests. Mild weakness of frowning was the only side effect, lasting 1–12 weeks and completely resolving in all patients. Although sweating has not yet recurred in most patients at follow-up periods up to 27 months, one patient had a relapse 9 months after treatment. Following reports on palmar and axillary hyperhidrosis and gustatory sweating (Frey's syndrome) this is apparently the first report on the use of BTX in the treatment of idiopathic craniofacial hyperhidrosis. BTX seems a promising new treatment for localized hyperhidrosis. Received: 24 August 1999 / Received in revised form: 13 March 2000 / Accepted: 7 June 2000