Breast reconstruction with abdominal flaps after abdominoplasties.

After the reported safe transverse rectus abdominis myocutaneous (TRAM) flap after liposuction of the abdomen, two cases of bipedicled reconstruction with this flap after abdominoplasty were successfully performed. This operation has not previously been considered possible because of the transection of the perforator arteries during the undermining of the abdomen. To examine the possible reperfusion of the perforator arteries, the authors studied the perforator arteries of 10 patients before they underwent abdominoplasty and at 1 week, 3 months, and 6 months after the operation. The arteries were studied with color-duplex scanning and power Doppler, using 10-MHz superficial probes, and their position was marked on a map. A cadaver study of a woman who had had an abdominoplasty 10 years before her death is also presented. In every patient, reperfusion of all perforator arteries was documented, starting from the control at 1 month. In no case was the caliber of the reperfused vessels more than 40 percent of the original diameter (maximum: 0.53 mm). This was also confirmed by the cadaver study. In conclusion, after an abdominoplasty operation, constant reperfusion of the perforator arteries of the rectus muscles occurs. However, the diameter of the arteries may not be enough to provide the necessary blood supply for a TRAM flap, which is therefore strongly discouraged by the authors after abdominoplasty in favor of a vertical rectus abdominis muscle (VRAM) flap. A liposuction, which does not necessarily disrupt the perforators, is not an absolute contraindication for a TRAM flap, provided that an accurate color-duplex scanning study is done.     

Benzodipyrazoles: a new class of potent CDK2 inhibitors

The synthesis and the preliminary expansion of this new class of CDK2 inhibitors are presented. The synthesis was accomplished using a solution-phase protocol amenable to rapid parallel expansion and suitable to be scaled-up in view of possible lead development. Following a medicinal chemistry program aimed at improving cell permeability and selectivity, a series of compounds with nanomolar activity in the biochemical assay and able to efficiently inhibit tumor cell proliferation has been obtained.     

Characterization of pearl millet prolamins

We report the physical-chemical characterization of the major alcohol-soluble proteins present in seeds of pearl millet (Pennisetum glaucum) by SDS-PAGE, bidimensional gel electrophoresis, MALDI-TOF/MS and RP-HPLC. We demonstrate the presence of three major prolamins, called A-, B- and C-pennisetin with mass values around 27, 22 and 12 kDa, respectively. We present partial amino acid sequences of these major proteins, which should allow the posterior isolation of the respective genes.     

Absence of the 9-bp deletion of mitochondrial DNA in pre-Hispanic inhabitants of Argentina

We investigated the incidence of the Region V mitochondrial DNA 9-base-pair (bp) deletion from human remains recovered from several archaeological sites and contexts throughout Argentina. Of the 34 samples analyzed, 24 yielded DNA extractions that gave clear amplification results. All of the individuals carried two repeats of the 9 bp, one of which has been shown to be deleted in some individuals of Asian origin and defines mitochondrial lineage B. Although most of the modern Amerindian groups in the region exhibit the deletion in high frequencies, the absence of the 9-bp deletion among ancient populations of South America seems to be the rule rather than the exception, as was reported by several studies involving extinct populations. The evidence gathered until now suggests that the earliest settlers of this region of South America did not carry mitochondrial lineage B.     

Diversity of Geotrichum candidum strains isolated from traditional cheesemaking fabrications in France

The diversity of French fungus-ripened cheeses is due partly to the succession of fungi that colonize the cheese during ripening. Geotrichum candidum appears in the early stages of ripening on soft cheeses such as Camembert and semihard cheeses such as St. Nectaire and Reblochon. Its lipases and proteases promote flavor development, and its aminopeptidases reduce bitterness imparted by low-molecular-weight peptides in cheese. We assessed the genetic diversity of G. candidum strains by using random amplification of polymorphic DNA (RAPD)-PCR correlated with phenotypic tests for carbon assimilation and salt tolerance. Strains were isolated from milk, curd, and cheese collected in seven major cheesemaking regions of France. Sixty-four isolates were characterized. We found high genetic diversity of G. candidum even within the same cheesemaking regions. Strains did not group according to region. All of the strains from the Haute-Savoie were able to assimilate lactate as the sole source of carbon, while lactate assimilation varied among strains from the Auvergne. Strains varied in D-mannitol assimilation, and none used citrate as the sole source of carbon. Yeast-like colony morphology predominated in Reblochon, while all of the strains isolated from St. Nectaire were filamentous. The RAPD-PCR technique readily differentiated Geotrichum fragrans isolated from milk and curd in a St. Nectaire cheesemaking facility. This study reveals an enormous diversity of G. candidum that has been empirically selected through the centuries by the cheesemakers of France.     

Carcinoma in chronic pressure sores: a fulminant disease process

Four cases of squamous cell carcinoma arising from chronic pressure sores in paraplegic and tetraplegic patients are presented and the literature reviewed. These pressure-sore carcinomas are characterized by a shorter latency period and a fulminant clinical course with a very high metastatic rate. Very aggressive treatment including even hemicorporectomy must be considered if a cure is to be achieved.     

Voltage sensitivities and deactivation kinetics of histamine H3 and H4 receptors

Agonist potency at some neurotransmitter receptors has been shown to be regulated by voltage, a mechanism which has been suggested to play a crucial role in the regulation of neurotransmitter release by inhibitory autoreceptors. Likewise, receptor deactivation rates upon agonist removal have been implicated in autoreceptor function. Using G protein-coupled potassium (GIRK) channel activation in Xenopus oocytes as readout of receptor activity, we have investigated the voltage sensitivities and signaling kinetics of the hH₃⁴⁴⁵ and hH₃³⁶⁵ isoforms of the human histamine H₃ receptor, which functions as an inhibitory auto- and heteroreceptor in the nervous system. We have also investigated both the human and the mouse homologues of the related histamine H₄ receptor, which is expressed mainly on hematopoietic cells. We found that the hH₃⁴⁴⁵ receptor is the most sensitive to voltage, whereas the hH₃³⁶⁵ and H₄ receptors are less affected. We further observed a marked difference in response deactivation kinetics between the hH₃⁴⁴⁵ and hH₃³⁶⁵ isoforms, with the hH₃³⁶⁵ isoform being five to six-fold slower than the hH₃⁴⁴⁵ receptor. Finally, using synthetic agonists, we found evidence for agonist-specific voltage sensitivity at the hH₄ receptor. The differences in voltage sensitivities and deactivation kinetics between the hH₃⁴⁴⁵, hH₃³⁶⁵, and H₄ receptors might be relevant to their respective physiological roles.     

Mandelic acid condensation polymer: novel candidate microbicide for prevention of human immunodeficiency virus and herpes simplex virus entry

Presently marketed vaginal barrier methods are cytotoxic and damaging to the vaginal epithelium and natural vaginal flora when used frequently. Novel noncytotoxic agents are needed to protect men and women from sexually transmitted diseases. One novel candidate is a mandelic acid condensation polymer, designated SAMMA. The spectrum and mechanism of antiviral activity were explored using clinical isolates and laboratory-adapted strains of human immunodeficiency virus (HIV) and herpes simplex virus (HSV). SAMMA is highly effective against all CCR5 and CXCR4 isolates of HIV in primary human macrophages and peripheral blood mononuclear cells. SAMMA also inhibits infection of cervical epithelial cells by HSV. Moreover, it exhibits little or no cytotoxicity and has an excellent selectivity index. SAMMA, although not a sulfonated or sulfated polymer, blocks the binding of HIV and HSV to cells by targeting the envelope glycoproteins gp120 and gB-2, respectively, and also inhibits HSV entry postattachment. SAMMA is an excellent, structurally novel candidate microbicide that warrants further preclinical evaluation.     

Cocaine produces D2R-mediated conformational changes in the adenosine A2AR-dopamine D2R heteromer

Adenosine A_2A receptors (A_2ARs) and dopamine D₂ receptors (D₂Rs) form constitutive heteromers in living cells and exhibit a strong functional antagonistic interaction. Recent findings give neurochemical evidence that extended cocaine self-administration in the rat give rise to an up-regulation of functional A_2ARs in the nucleus accumbens that return to baseline expression levels during cocaine withdrawal. In the present work, the acute in vitro effects of a concentration of cocaine known to fully block the dopamine (DA) transporter without exerting any toxic actions were investigated on A_2AR and D_2LR formed heteromers in transiently co-transfected HEK-293T cells. In vitro treatment of cocaine was found to produce changes in D₂R homodimers and in A_2AR-D₂R heterodimers detected through bioluminescent energy transfer (BRET). Cocaine was found to produce a time- and concentration-dependent reduction in the BRET_max between A_2AR-D_2LR heterodimers and D_2LR homodimers, but not A_2AR homodimers, indicating its effect on D₂R. Cocaine was evaluated with regard to D₂R binding using a human D_2LR stable expressing CHO cell line and was found to produce an increase in the affinity of hD_2LR for DA. At the level of G protein-coupling, cocaine produced a small, but significant increase in DA-stimulated binding of GTPγS. However, cocaine failed to modulate D₂R agonist-induced inhibition of cAMP in stable hD_2LR CHO cells or the gating of GIRK channels in oocytes. Taken together, these results indicate a direct and specific effect of a moderate concentration of cocaine on the DA D_2LR, that results in enhanced agonist recognition, G protein-coupling and an altered conformational state of D₂R homodimers and A_2AR-D₂R heterodimers.