Ictal chronology and interictal spikes predict perfusion patterns in temporal lobe epilepsy: a multivariate study.

Typical (TPP) and atypical (APP) perfusion patterns (PP) may be seen in ictal SPECT of patients with temporal lobe epilepsy (TLE). APP may pose problem in the lateralization of the epileptogenic zone (EZ). We aimed to investigate predictive variables for the occurrence of TPP and APP. Fifty-one TLE patients were submitted to successful anterior-mesial temporal lobectomy. Univariate (UVA) and multivariate (MVA) analysis were performed upon clinical data, distribution of interictal spikes, and ictal chronology of seizures. From MVA, a final predictive model (FPM) was determined to better predict TPP and APP. Forty patients showed TPP (78.5%) and 11 patients APP (21.5%). Accuracy of ictal SPECT was higher in the unilateral (UIS) than in the bilateral (BIS) interictal spikes group (P = 0.05). FPM showed that patients exhibiting BIS, with shorter proportion of the electrographic seizure occurring after completion of tracer injection, and longer clinical than EEG seizure duration had more APP (P = 0.003). Generalized tonic-clonic seizures did not result in more APP. We concluded that analysis of ictal SPECT in TLE requires the knowledge of TPP and APP, the distribution of interictal spikes on temporal lobes and the ictal chronology of seizures. BIS showed that beyond a more complex epileptogenicity and seizure propagation, they may also lead to APP.     

Metabolic products of microorganisms. 255. Nikkomycins Wz and Wx, new chitin synthetase inhibitors from Streptomyces tendae

Two new dipeptidyl nikkomycins of the Z and X type were isolated from the culture broth of Streptomyces tendae TU 901/395-11/32 and characterized. They show a variation in the amino acid moiety of the molecule. Nikkomycin Wz is composed of L-tyrosine and 5-amino-5-deoxy-D-allo-furanuronic acid N-glycosidally bound to uracil, whereas nikkomycin Wx is composed of L-tyrosine and 5-amino-5-deoxy-D-allo-furanuronic acid N-glycosidally bound to 4-formyl-4-imidazolin-2-one. The new nikkomycins are good inhibitors of chitin synthetase from Coprinus cinereus but they did not inhibit growth of fungi and yeasts.     

Extracorporeal piezoelectric gallstone lithotripsy: initial surgical experience with a new treatment. Technique and indications

The extracorporeal piezoelectric lithotripsy (EPL) is a new method for non-operative therapy of symptomatic gallbladder and problematic bile duct stones. The rare intrahepatic calculi were similarly disintegrated. Best results were reached with EPL as adjuvant measure or combined with oral cheno- and ursodeoxycholic acid therapy. EPL compared to other lithotripsy techniques is performed without any analgesia. That means advantage and patient's benefit.     

Molecular basis of the functional podocin-nephrin complex: mutations in the NPHS2 gene disrupt nephrin targeting to lipid raft microdomains

Hereditary nephrotic syndrome is a heterogeneous disease, characterizedby heavy proteinuria and renal failure. Mutations of NPHS1 orNPHS2, the genes encoding for nephrin and podocin, lead to earlyonset of heavy proteinuria, and rapid progression to end-stagerenal disease, suggesting that both proteins are essential forthe integrity of the glomerular filter. Podocin is a stomatinprotein family member with a predicted hairpin-like structurelocalizing to the insertion site of the slit diaphragm of podocytes,the visceral glomerular epithelial cells of the kidney. Herewe investigate the pathomechanisms of different disease-causingpodocin mutations. We show that wild-type podocin is targetedto the plasma membrane, and forms homo-oligomers involving thecarboxy and amino terminal cytoplasmic domains. The associationof podocin with specialized lipid raft microdomains of the plasmamembrane was a prerequisite for recruitment of nephrin intorafts. In contrast, disease-causing mutations of podocin (R138Qand R138X) failed to recruit nephrin into rafts either becausethese mutants were retained in the endoplasmic reticulum (R138Q),or because they failed to associate with rafts (R138X) despitetheir presence in the plasma membrane. None of the mutants didaugment nephrin signaling, suggesting that lipid raft targetingfacilitates nephrin signaling. Our findings demonstrate thatthe failure of mutant podocin to recruit nephrin into lipidrafts may be essential for the pathogenesis of NPHS2. ^* To whom correspondence should be addressed. Tel: +49 7612703559;Fax: +49 7612706362; Email: benzing{at}med1.ukl.uni-freiburg.de      

Evaluation of the osmoregulatory function of taurine in brain cells

Summary Homogenous primary cultures of mouse astrocytes and cortical neurons were used to clarify the role of taurine in ion and osmoregulation in the CNS. This study indicates that both neurons and glial cells have uptake systems for taurine. The cell water content does not change during loading of cells with taurine. Chemical analysis indicates that part of the accumulated taurine is metabolized and that the product(s) are stored in the cells. Extracellular taurine (1 mM) has no effect on K⁺, Na⁺, Cl^-, or Ca²⁺ movements in astrocytes. However, astrocytes loaded to a taurine content which corresponds a concentration of 60 mM (corresponds to normal mouse cortex levels) show a 50% reduction in their K⁺ accumulation by carriers and a 100% increase in Ca²⁺ turnover rates. Movements of Ca²⁺ and K⁺ are involved in neurotransmission. It appears that taurine stored in glial cells, has an important effect on ion homeostasis in the CNS and may act indirectly on neuronal excitability.     

Irritant actions of unphysiological pH values. A controlled procedure to test for topical irritancy

The abdominal skin of juvenile white mice was used. Topical application was accomplished by intracutaneou injection. The solutions tested were thoroughly standardized. By using a special buffer system, a mixture of histidine glutamate and lysine glutamate, each pH value could be tested with the same buffer capacity. The pH values varied from pH 3 to pH 11, the solutions being always isoosmolalic with plasma.Two criteria were used to judge the irritancy: (a) the edematous reaction for the first 6 h and (b) the macroscopic aspect after 24 h. A very special procedure enabled us to obtain objective numerical values for criterion (a).The results disclose that irritation becomes manifest at pH 4 and pH 10, becomes clear-cut with pH 3 and even more so with pH 11, and depends strongly on the buffer capacity employed.With two substances — amidosulfuric acid and (tri) sodium phosphate — it was exemplified how the procedure could be used to routinely screen for topical irritancy in an informative, inexpensive and decent manner.This work was encouraged and financially supported by the Swiss Federal Office of Health, Section Toxicology.     

Human melanoma progression in skin reconstructs : biological significance of bFGF

Human skin reconstructs are three-dimensional in vitro models consisting of epidermal keratinocytes plated onto fibroblast-contracted collagen gels. Cells in skin reconstructs more closely recapitulate the in situ phenotype than do cells in monolayer culture. Normal melanocytes in skin reconstructs remained singly distributed at the basement membrane which separated the epidermis from the dermis. Cell lines derived from biologically early primary melanomas of the radial growth phase proliferated in the epidermis and the basement membrane was left intact. Growth and migration of the radial growth phase melanoma cells in the dermal reconstruct and tumorigenicity in vivo were only observed when cells were transduced with the basic fibroblast growth factor gene, a major autocrine growth stimulator for melanomas. Primary melanoma cell lines representing the more advanced stage vertical growth phase invaded the dermis in reconstructs and only an irregular basement membrane was formed. Metastatic melanoma cells rapidly proliferated and aggressively invaded deep into the dermis, with each cell line showing typical invasion and growth characteristics. Our results demonstrate that the growth patterns of melanoma cells in skin reconstructs closely correspond to those in situ and that basic fibroblast growth factor is critical for progression.