No abstract

A double blind crossover study with placebo and earbamazepine was done in 30 diabetic patients who presented diverse clinical types of peripheral diabetic neuropathy. The active drug offered symptomatic relief of aH sensory manifestations in 28 cases. No effort was made to assess the action of carbamazepine upon motor or visceral manifestations of neuropathy. There were two complete failures. Untoward effects were frequent but usually mild and transient; two patients presented a rash that required discontinuation of the drug.

No abstract

The potassium channel toxin secreted by the sea anemone Bunodosoma granulifera (BgK) is a 37‐amino‐acid peptide containing three disulfide bridges. Because a synthetic peptide corresponding to the reported sequence of BgK was found not to fold properly, the sequence was determined again. The new sequence differed from the previous one in the C‐terminal tetrapeptide, which contains two cysteines involved in disulfide bridging. The revised sequence is: V C R D W F K E T A C R H A K S L G N C R T S Q K Y R A N C A K T C E L C. The toxin BgK was synthesized according according to the new sequence and folded successfully. Disulfide bridges were assigned by peptide mapping on both natural and synthetic forms to be between Cys2‐Cys37, Cys11‐Cys30 and Cys20‐Cys34. The toxin contains a C‐terminal free carboxylate as shown by comparing the native toxin with two synthetic peptides containing the C‐terminus in either the carboxylate or carboxamido form. Synthetic BgK inhibits binding of 125I‐α‐dendrotoxin to rat brain synaptosomal membranes, similarly to natural BgK (nanomolar range). No activity was observed on maxi‐K+ channels incorporated into planar lipid bilayers. The ability of BgK to block voltage‐dependent K+ channels was determined from recordings of whole cell currents in Xenopus oocytes injected with cRNA encoding three cloned Kv1 channels (Kv1.1, Kv1.2, Kv1.3) and one Kv3 (Kv3.1) channel. The Shaker‐related Kv1 channels are equally affected by BgK, while the Shaw‐related channel Kv3.1 is insensitive up to 0.125 pM toxin. Indeed, half blockage of the current through the three Kv1 channels tested occurred in the same concentration range (Kd= 6 nM for Kv1.1, 15 nM for Kv1.2, 10 nM for Kv1.3). The specificity of BgK for the Shaker‐related K+ channels indicates that BgK is able to discriminate a large group of neuronal Kv1 channels in situ. The sequence, the disulfide bridge pattern, the secondary structure and the biological activity of BgK demostrated that the sea anemone toxins, i.e. BgK, ShK and Kaliseptine, constitute novel molecular probes useful for investigating K+ channel properties.

Epidemiologic studies have emphasized the close relationship between high BP and cardiovascular disease (CVD). Recently published prospective studies have focus on systolic and pulse pressure (PP). Systolic BP seems to be a more important factor than diastolic BP on cardiovascular and all-cause mortality in older patients. PP reflects stiffness of the large arteries and increases with age. Increasingly, PP is recognized as an independent predictor of myocardial infarction, congestive heart failure, and cardiovascular death, even in hypertensive patients who undergo successful antihypertensive drug therapy, especially in older individuals. Chronic kidney disease (CKD) is a major public health problem. The progression of kidney disease and its associated cardiovascular complications are the major causes of morbidity and mortality. This holds true for all stages of kidney disease, including ESRD that requires renal replacement therapy. C hronic kidney disease (CKD) is a worldwide public health problem. There is a rising incidence and prevalence of ESRD, with poor outcome and high cost. ESRD that requires treatment with dialysis or transplantation is the most visible outcome of CKD. However, cardiovascular disease (CVD) also frequently is associated with CKD, which is important because individuals with CKD are more likely to die of CVD than to develop ESRD (1). CVD in CKD is treatable and potentially preventable, and CKD seems to be a risk factor for CVD (2). In 1998, the National Kidney Foundation Task Force issued a report that emphasized the high risk for CVD in CKD (3). This report showed that there was a high prevalence of CVD in CKD and that mortality as a result of CVD was 10 to 30 times higher in dialysis patients than in the general population. The task force recommended that patients with CKD be considered in the highest risk group. Go et al. (4) demonstrated that reduced estimated GFR Ͻ60 ml/min per 1.73 m 2 independently predicts the risk for death and cardiovascular events in individuals with or without known CVD.Most of the traditional CVD risk factors, such as older age, diabetes, systolic hypertension, left ventricular hypertrophy, and low HDL cholesterol, are highly prevalent in CKD. Several nontraditional factors, such hyperhomocysteinemia, oxidant stress, dyslipidemia, and elevated inflammatory markers, are associated with atherosclerosis. Oxidant stress and inflammation may be the primary mediators or the "missing link" that could explain the tremendous burden of CVD in CKD (2). The purpose of this review is to show the importance of pulse pressure (PP) as clinical marker of cardiovascular risk in patients with CKD. PP as Cardiovascular Risk FactorThe principal components of BP consist of both a steady component (mean arterial pressure [MAP]) and a pulsatile component (PP). Major determinants of MAP are ventricular ejection and peripheral vascular resistance. PP, the difference between systolic BP (SBP) and diastolic BP (DBP), also is made up of two major components: One that is caused by ventri...