Enzymes involved in l-lactate metabolism in humans.

l-lactate formation occurs via the reduction of pyruvate catalyzed by lactate dehydrogenase. l-lactate removal takes place via its oxidation into pyruvate, which may be oxidized or converted into glucose. Pyruvate oxidation involves the cooperative effort of pyruvate dehydrogenase, the tricarboxylic acid cycle, and the mitochondrial respiratory chain. Enzymes of the gluconeogenesis pathway sequentially convert pyruvate into glucose. In addition, pyruvate may undergo reversible transamination to alanine by alanine aminotransferase. Enzymes involved in l-lactate metabolism are crucial to diabetes pathophysiology and therapy. Elevated plasma alanine aminotransferase concentration has been associated with insulin resistance. Polymorphisms in the G6PC2 gene have been associated with fasting glucose concentration and insulin secretion. In diabetes patients, pyruvate dehydrogenase is down-regulated and the activity of pyruvate carboxylase is diminished in the pancreatic islets. Inhibitors of fructose 1,6-bisphosphatase are being investigated as potential therapy for type 2 diabetes. In addition, enzymes implicated in l-lactate metabolism have revealed to be important in cancer cell homeostasis. Many human tumors have higher LDH5 levels than normal tissues. The LDHC gene is expressed in a broad range of tumors. The activation of PDH is a potential mediator in the body response that protects against cancer and PDH activation has been observed to reduce glioblastoma growth. The expression of PDK1 may serve as a biomarker of poor prognosis in gastric cancer. Mitochondrial DNA mutations have been detected in a number of human cancers. Genes encoding succinate dehydrogenase have tumor suppressor functions and consequently mutations in these genes may cause a variety of tumors.

Open analogues of arcyriaflavin A. Synthesis through Diels-Alder reaction between maleimides and 1-aryl-3-tert-butyldimethylsiloxy-1, 3-butadienes.

The preparation of a range of open analogues of arcyriaflavin A is described. The synthetic approach is based on the use of perhydroisoindole-1,3,5-triones as key intermediates, which were obtained via Diels-Alder methodology using 1-aryl-3-siloxy-1, 3-butadienes as starting materials. Fischer indolization and aromatization processes afforded different methoxy-substituted arylpyrrolocarbazoles. The stereochemistry and conformation of the Diels-Alder products and the regiochemistry of the indolization reactions are supported by NMR and molecular modeling studies.

[Triple association of mesencephalic syndromes]. / Triple asociación de síndromes mesencefálicos.

INTRODUCTION: The mesencephalic alternating syndromes or syndromes of Weber, Benedikt and Claude are uncommon in clinical practice. They are caused by a lesion in the mesencephalus which affects the third cranial nerve bundle, together with the corticospinal pathway, subthalamic nucleus and the dentato-rubric path. CLINICAL CASE: We present the case of a normotensive patient who, as a consequence of a hematoma in the mesencephalic tegmentum, had the association of these three syndromes consecutively. The clinical course was favorable, so that after three months of follow-up only paralysis of the third cranial nerve bundle persisted. DISCUSSION: In the syndromes of Weber, Benedikt and Claude there is the association of ophthalmoplegia with hemiplegia, or a cerebellar hemisyndrome or contralateral abnormal movements compatible with hemiballismus, respectively. Amongst the commonest causes are expansive processes, tumors and arteriovenous malformations. More rarely they are due to cerebrovascular accidents, which are usually ischemic and occasionally hemorrhagic in aetiology. CONCLUSIONS: Spontaneous mesencephalic hematomas are infrequent. They make up approximately 1% of all intracranial hematomas. The commonest site is the tegmentum followed by the peduncle and tectum. They have better prognosis than other hematomas of the brainstem.

[Multiple cranial neuropathy: an atypical variant of the Guillain-Barre syndrome?]. / Neuropatía craneal múltiple: una variante atípica del síndrome de Guillain-Barré?

INTRODUCTION: Multiple cranial neuropathy or polineuritis cranealis is rarely seen in everyday clinical practice. It is considered to be a topographically circumscribed form of the Guillain-Barré syndrome. The cases described have a wide range of clinical and biological characteristics. Some of these may be due to infectious agents. CLINICAL CASE: We present the case of a 50 year old man with acute onset of diplopia, dysphagia, anarthria, cervical and right arm flexor-extensor muscle weakness due to involvement of many motor cranial nerves and superior cervical nerve roots. On neurological examination there was mixed involvement, mainly of the axons of the nerve trunks involved. Studies to determine aetiology did not show any demonstrable agent. DISCUSSION AND CONCLUSIONS: Different topographical varieties of the Guillain-Barré syndrome have been described, including: Fisher's syndrome, pharyngo-cervico-brachial paralysis, arreflexive paraparesia, bilateral facial paralysis with paraesthesias, hyporeflexia and bilateral lumbar polyradiculopathy. We compare the clinical characteristics of our patient with those described in the literature. We found a degree of heterogenicity in the clinical and biological characteristics of the cases described, which may mean that they had different aetiologies. Therefore, we consider that before labelling these conditions as atypical variants of the Guillain-Barré syndrome, a thorough search should be made for a precise aetiology.

[Complete axonotmesis of the axillary nerve in relation to microtrauma]. / Axonotmesis completa del nervio axilar en relación con un microtraumatismo.

INTRODUCTION: The axillary nerve is injured in many clinical situations, mainly in major surgical or traumatic lesions of the shoulder. Equally, it may be found in the context of microtraumatisms or compressive mechanisms. Amyotrophic neuralgia is a clinical entity with pain and later atrophy of the muscle which affects various nerves and nerve groups, as shown by neurophysiological studies. CASE REPORT: We present a lesion with complete axonotmesis of the axillary nerve with a time-relationship to microtraumatism. Initially the patient complained of some pain in the shoulder. During follow-up striking atrophy of the deltoid muscle was seen. CONCLUSIONS: We have reviewed the mechanisms described for lesions of the axillary nerve, which do not include the one we found. We discuss the possibility of our case being included in the clinical group described as having amyotrophic neuralgia, although there are some neurophysiological findings which are not typical of this condition. We suggest a review of the many possible trigger factors described in the genesis of amyotrophic neuralgia. Possibly some cases with atypical histories of trauma, and lesions shown by neurophysiological studies to be particularly severe, may be separated from this group.

Delayed graft function after renal transplantation in patients undergoing peritoneal dialysis and hemodialysis.

We have compared the incidence of delayed graft function (DGF) after renal transplantation in our patients undergoing peritoneal dialysis (PD) (group A, n = 92) or hemodialysis (HD) (group B, n = 587), analyzing the prevalence of the main risk factors for DGF in both groups. Both groups were comparable, except for a higher prevalence of diabetes (p < 0.05) and a shorter time on dialysis (p < 0.01) in group A. Immediate graft function occurred in 68.5% of group A and 46.5% of group B, DGF in 22.5% of group A and 39.5% of group B, and there was never any function in 9% of group A and 14% of group B (p < 0.001). When potential risk factors for DGF were compared, no relevant differences could be found. HD was performed more frequently immediately before surgery in group B (p < 0.001), but statistical analysis showed no impact of this measure on the incidence of DGF. In conclusion, in our population, patients on PD present higher rates of immediate graft function after renal transplantation than patients on HD. The explanation for the difference is not clear, but seems to be related to the dialysis modality itself, as the profile of risk factors for DGF is very similar in both populations.

Survival on chronic peritoneal dialysis: have results improved in the 1990s?

One hundred and seventy patients were treated with home peritoneal dialysis (PD) in our unit between 1986 and 1994. During this time lapse, several technical improvements were included in our practice. Among others there were: Swan neck permanent catheters, Y-systems, and automated home PD (APD). We reviewed our experience, to assess if these improvements had any impact on patient and technique survival, comparing patients who started PD between 1986 and 1989 (group A), with those who started PD between 1990 and 1994 (group B). Both groups had a comparable basal comorbidity, except for a higher proportion of elderly patients in group B (mean age 48 vs 58 years, p < 0.01). The incidence of peritonitis was lower in group B, while there were no differences in the rates of catheter-related infection or hospital admission. Also, there were no significant differences in patients or technique survival. The increasing presence of elderly patients in our PD unit was, apparently, determinant for the evolution of patient survival. On the other side, technical improvements had a marginal impact on technique survival. A good general PD survival in both groups, with few patients changing to hemodialysis (HD), may explain the lack of significant differences. In addition, peritonitis and inadequate PD/ultrafiltration (UF) were replaced by abdominal surgical events and social reasons as the main causes for PD failure in the second phase of the study.

Treatment of Staphylococcus aureus nasal carriers in continuous ambulatory peritoneal dialysis with mupirocin: long-term results.

We present the clinical results of a prospective protocol of the treatment of Staphylococcus aureus nasal carriers (SANCs) in our continuous ambulatory peritoneal dialysis unit with mupirocin (Bactroban, SmithKline Beecham Pharmaceuticals, Philadelphia, PA). We monitored the incidence of peritonitis and catheter exit-site infection, the rate of infection-related catheter loss, and the degree of association between SANC state and S aureus infection. The study group included 94 patients with a follow-up of 1,097 patient-months (phase B). The same information was retrospectively collected among 74 continuous ambulatory peritoneal dialysis patients treated during the 24 months preceding the study period (follow-up of 1,043 patient-months) (phase A). S aureus nasal carriage was observed in 47.5% of the patients. Mupirocin was very effective in eradicating S aureus from the nares, but most patients required periodic retreatment. The incidence of S aureus peritonitis decreased from 1 episode/58 patient-months in phase A to 1 episode/548 patient-months in phase B, and the incidence of exit-site infection decreased from one episode/55 patient-months in phase A to 1 episode/137 patient-months in phase B. However, there was a simultaneous increase in the incidence of infections by other gram-positive and -negative bacteria. The rate of catheter loss after peritonitis (P = not significant) or exit-site infection (P < 0.05) tended to decrease from phase A to phase B. Seventy-seven percent of the peritonitis infections and 74% of the exit-site infections by S aureus occurred in SANCs.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of peritonitis in CAPD with ciprofloxacin: long-term experience.

We present the long-term results of a protocol of empirical monotherapy of continuous ambulatory peritoneal dialysis (CAPD)-related peritonitis with ciprofloxacin. One hundred and fifteen episodes of peritonitis were studied. The treatment protocol included 5 days of intraperitoneal (IP) administration of the drug, followed by 10 days of oral therapy. A good clinical response was obtained in 83% of the cases, while treatment failure was observed in 4% and relapse in 7%. A decrease in the sensitivity to ciprofloxacin of the peritonitis agents was observed in the study, with Staphylococcus spp. in particular. Three episodes of peritonitis due to bacteria resistant in vitro to ciprofloxacin responded to the treatment protocol. Ciprofloxacin attained good plasma levels both after oral and IP administration. However, dialysate levels were poor after oral administration. The most frequent side effect was gastric intolerance to oral ciprofloxacin. Two patients experienced severe adverse reactions to the drug. Ciprofloxacin may be a good choice for empirical monotherapy of CAPD-related peritonitis. However, the emergence of bacterial resistances must be carefully monitored. The drug should be administered intraperitoneally, at least to induce remission of the infection. Side effects are not frequent, but ciprofloxacin should not be considered an innocuous drug.