Peripheral vestibular plasticity vs central compensation: evidence and questions.

Over the last few decades, several studies have been conducted to identify the mechanisms involved in spontaneous functional recovery following peripheral vestibular damage. Different reactive processes occur at both the central and peripheral levels over the first few hours after the loss of the peripheral vestibular input. The restoration of the electrophysiological homeostasis between opposite vestibular nuclei is one of the key mechanisms of central compensation. This is achieved through a mosaic of biochemical events within the vestibular nuclei that each occur with their own kinetics. At the same time, under specific conditions, strong synaptic plasticity may take place within the vestibular sensory organs. It is thought that this reactive plasticity can contribute to the repair of damaged contacts between hair cells and fibres of the vestibular nerve, thus gradually restoring peripheral sensory input. These different plastic phenomena seem to reproduce those observed during development. Research is now needed to identify the cellular and molecular mechanisms that support this spontaneous peripheral repair process, with the ambition 1 day to be able to control it and stimulate the restoration of gait and balance.

New mouse model for inducing and evaluating unilateral vestibular deafferentation syndrome.

BACKGROUND: Unilateral vestibular deafferentation syndrome (uVDS) holds a particular place in the vestibular pathology domain. Due to its suddenness, the violence of its symptoms that often result in emergency hospitalization, and its associated original neurophysiological properties, this syndrome is a major source of questioning for the otoneurology community. Also, its putative pathogenic causes remain to be determined. There is currently a strong medical need for the development of targeted and effective countermeasures to improve the therapeutic management of uVDS. NEW METHODS: The present study reports the development of a new mouse model for inducing and evaluating uVDS. Both the method for generating controlled excitotoxic-type peripheral vestibular damages, through transtympanic administration of the glutamate receptors agonist kainate (TTK), and the procedure for evaluating the ensuing clinical signs are detailed. COMPARISON WITH EXISTING METHODS: Through extensive analysis of the clinical symptoms characteristics, this new animal model provides the opportunity to better follow the temporal evolution of various uVDS specific symptoms, while better appreciating the different phases that composed this syndrome. RESULTS: The uVDS evoked in the TTK mouse model displays two main phases distinguishable by their kinetics and amplitudes. Several parameters of the altered vestibular behaviour mimic those observed in the human syndrome. CONCLUSION: This new murine model brings concrete information about how uVDS develops and how it affects global behaviour. In addition, it opens new opportunity to decipher the etiopathological substrate of this pathology by authorizing the use of genetically modified mouse models.

Protection of Human Pancreatic Islets from Lipotoxicity by Modulation of the Translocon.

Type 2 diabetes is characterized by peripheral insulin resistance and pancreatic beta cell dysfunction. Elevated free fatty acids (FFAs) may impair beta cell function and mass (lipotoxicity). Altered calcium homeostasis may be involved in defective insulin release. The endoplasmic reticulum (ER) is the major intracellular calcium store. Lipotoxicity induces ER stress and in parallel an ER calcium depletion through unknown ER calcium leak channels. The main purposes of this study is first to identify one of these channels and secondly, to check the opportunity to restore beta cells function (i.e., insulin secretion) after pharmacological inhibition of ER calcium store depletion. We investigated the functionality of translocon, an ER calcium leak channel and its involvement on FFAs-induced alterations in MIN6B1 cells and in human pancreatic islets. We evidenced that translocon acts as a functional ER calcium leak channel in human beta cells using anisomycin and puromycin (antibiotics), respectively blocker and opener of this channel. Puromycin induced a significant ER calcium release, inhibited by anisomycin pretreatment. Palmitate treatment was used as FFA model to induce a mild lipotoxic effect: ER calcium content was reduced, ER stress but not apoptosis were induced and glucose induced insulin secretion was decreased in our beta cells. Interestingly, translocon inhibition by chronic anisomycin treatment prevented dysfunctions induced by palmitate, avoiding reticular calcium depletion, ER stress and restoring insulin secretion. Our results provide for the first time compelling evidence that translocon actively participates to the palmitate-induced ER calcium leak and insulin secretion decrease in beta cells. Its inhibition reduces these lipotoxic effects. Taken together, our data indicate that TLC may be a new potential target for the treatment of type 2 diabetes.

Dorsolateral striatum and dorsal hippocampus: a serial contribution to acquisition of cue-reward associations in rats.

In laboratory rodents, procedural and declarative-like memory processes are often considered operating in dual, sometimes even competing with each other. There is evidence that the initial approach of a repetitive task first engages a hippocampus-dependent declarative-like memory system acquiring knowledge. Over repetition, there is a gradual shift towards a striatum-dependent response memory system. In the current experiment, Long-Evans male rats with bilateral, fiber-sparing ibotenic acid-induced lesions of the dorsolateral striatum or the dorsal hippocampus were trained in an olfactory associative task requiring the acquisition of both a procedural and a declarative-like memory. Rats with dorsolateral striatum lesions, and thus an intact hippocampus, were impaired on both sub-categories of memory performance. Rats with dorsal hippocampal lesions exhibited a substantial deficit in learning the declarative-like cue-reward associations, while the acquisition of the procedural memory component of the task was not affected. These data suggest that the dorsolateral striatum is required to acquire the task rule while the dorsal hippocampus is required to acquire the association between a given stimulus and its associated outcome. The finding is that the dorsolateral striatum and the dorsal hippocampus most probably contribute to successful learning of cue-reward associations in a sequential (from procedural to declarative-like memory) order using this olfactory associative learning task.

Prophylactic antimicrobials in elective colorectal and biliary surgery.

In 97 patients undergoing elective biliary (44) or colorectal (53) surgery, cases were randomly allocated to receive peri-operative prophylaxis with either cefoxitin (Mefoxin; MSD) or metronidazole, penicillin and tobramycin (MPT). Sepsis occurred in 3 of the biliary cases (6,8%) and in 16 of the colorectal cases (30,2%). In the colorectal group sepsis occurred equally in patients receiving cefoxitin (22,2%) or MPT (38,5%) (P = 0,20). Patients who developed sepsis did not have a prolonged hospital stay; strict criteria were used to define sepsis in this study and this explains the apparently high sepsis rate. A positive wound culture at the end of the operation was more common after colorectal surgery (30,2%) than after biliary surgery (4,6%) and was associated with a higher subsequent infection rate (P = 0,02).

Treatment of neutropenic infection: a randomized trial comparing latamoxef (moxalactam) with cephradine plus tobramycin.

Sixty neutropenic patients with infection were studied in a randomized trial comparing treatment with latamoxef (moxalactam) alone or with cephradine and tobramycin. The two treatment groups were comparable in respect to their clinical sites of infection, degree of neutropenia underlying malignancy, and organisms. Forty-two bacterial isolates were obtained from various clinically infected sites. All but two of these isolates were sensitive to latamoxef (30 highly sensitive, ten moderately sensitive). In contrast 29 of the isolates were resistant to cephradine and eight were resistant to both cephradine and tobramycin. Control of infection was achieved in 72% of patients treated with latamoxef and 55% treated with cephradine plus tobramycin. Latamoxef appears to be an effective antibiotic for the treatment of neutropenic patients with infection.

Haemoglobin Leiden in a South African negro. A case report.

A Black patient in whom an acute febrile illness was followed by a haemolytic crisis is presented. Investigation of the haemolytic anaemia showed the presence of an unstable haemoglobin which was found to be haemoglobin Leiden. Those members of the family who were available for investigation also had the unstable haemoglobin but showed no haemolysis. Radio-isotope studies on the patient confirmed haemolysis but showed that the spleen was not the main site of cell destruction.

Comparative in vitro appraisal of piperacillin, including its activity against Salmonella typhi.

Piperacillin was evaluated in vitro against 711 clinical isolates of aerobic and anerobic gram-positive and gram-negative bacteria, including 76 isolates of Salmonella typhi. Piperacillin minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were compared with those of a range of beta-lactam, aminoglycoside, and other antimicrobial agents, and inoculum size effects were considered. The relationship between dilution and disk diffusion tests was studied by regression analysis. In addition, piperacillin was assessed in combination with aminoglycoside and other beta-lactam drugs. This investigation has confirmed the activity of piperacillin against a broad range of bacteria, including Pseudomonas, Enterobacteriaceae, Neisseria, beta-lactamase-negative Haemophilus influenzae, and Staphylococcus aureus as well as enterococci, Bacteroides fragilis, and other anaerobes. All strains of Pseudomonas aeruginosa were inhibited by

The effect of prophylactic tinidazole on the anaerobic vaginal flora in patients undergoing gynaecological surgery.

The effects of prophylactic tinidazole on the vaginal carrier state of anaerobic bacteria and the development of postoperative infections were studied in 50 patients undergoing gynaecological surgery. The results are based on a double-blind trial, using tinidazole (Fasigyn; Pfizer) and placebo. Although no postoperative infections other than urinary tract infections were observed in our series, this study shows conclusively that the isolation of anerobic bacteria from the vagina decreased markedly in the tinidazole group compared with the placebo group.

Etiology of infantile enteritis in South Africa.

Infantile enteritis constitutes a major health problem in developing countries. Several investigations into the etiology of this condition among various South African populations have been undertaken during the past few years. Recent studies of black urban infants have revealed that salmonellae, shigellae, enterotoxigenic Enterobacteriaceae, and rotaviruses play a relatively minor role in infantile enteritis. On the other hand, all studies, including a number performed several years ago, have demonstrated that Escherichia coli strains belonging to traditional enteropathogenic serotypes are more frequently recovered from patients with diarrhea than from matched control subjects. These bacteria are particularly prominent during the summer months at the height of the annual gastroenteritis epidemic. Recent studies have indicated the importance of Campylobacter fetus in infantile enteritis, especially in children younger than nine months. The data point to a complex multiple etiology of infantile enteritis in South Africa, which will require clarification before specific preventive measures can be instituted.

Haemophilus endocarditis. A report of two cases.

Two cases of infective endocarditis caused by Haemophilus species are presented. Salient features were the following: occurrence in young adults, presence of underlying valvular disease, and presumptive diagnosis of renal artery embolism in one patient and petechial haemorrhages in the other. Recent reports of an increasing number of cases of infective endocarditis caused by Haemophilus species prompted us to report these 2 cases.