A novel copper (II) PAmPiCaT complex (cPAmPiCaTc) as a biologically potent candidate: A contraption evidence against methicillin-resistant Staphylococcus aureus (MRSA) and a molecular docking proof.

Increasing in the alarm against the resistant bacteria due to the failure of antibiotics, thereby the need of more efficiency/potent molecule to treat infections. In the present investigation, series of piperazine derivatives 5(a-l) compounds were synthesized and they were characterised by different spectral techniques such as 1H NMR, 13C NMR, IR and LCMS. A novel copper complex (cPAmPiCaTc) was developed for the first time by using potent analog 5e and characterized by IR and LCMS. The cPAmPiCaTc evaluated for antibacterial activity and showed excellent antimicrobial effect (12 ±â€¯0.08 mm, ZOI) at MIC 20 µg/mL against MRSA compared to standard antibiotics streptomycin and bacitracin at MIC 10 µg/mL. The results show promising anti-staphylococcal action against MRSA which confirmed by membrane damage, bioelectrochemistry, gene regulation (SarA and DHFR), and in silico molecular docking studies. Further, the cPAmPiCaTc also showed excellent blood compatibility and this result pave the way for interesting metallodrug therapeutics in future against MRSA infections.

New approach to address antibiotic resistance: Miss loading of functional membrane microdomains (FMM) of methicillin-resistant Staphylococcus aureus (MRSA).

The synthesized potent piperazine analog ChDiPiCa was characterised by various spectroscopic techniques and for the first time evaluated functional membrane microdomain (FMM) disassembly in methicillin-resistant Staphylococcus aureus (MRSA). The ChDiPiCa showed excellent in vitro biocidal activity against MRSA at 26 µg/mL compared to the antibiotic streptomycin and bacitracin 14 µg/mL and 13 µg/mL at 10 µg concentration respectively. The membrane damaging property was confirmed by the SEM analysis. Further, we addressed the new approach for the first time to overcome antibiotic resistance of MRSA through membrane microdomain miss loading to lipids. By which, the ChDiPiCa confirms the significant activity in miss loading of FMM of MRSA which is validated by the fatty acid profile and lipid analysis. The result shows that, altered saturated (Lauric acid and Myristic acid), mono unsaturated (Oleic acid), and poly unsaturated (Linoleic acid and Linolenic acid) fatty acids and hypothesises, altered the membrane functional lipids. For the better understanding of miss loading of FMM by the ChDiPiCa, the in-silico molecular docking studies was analyzed and confirmed the predicted role. This suggests the way to develop ChDiPiCa in medicinal chemistry as anti-MRSA candidates and also this report opens up new window to treat microbial pathogens and infections.

Role of BP*C@AgNPs in Bap-dependent multicellular behavior of clinically important methicillin-resistant Staphylococcus aureus (MRSA) biofilm adherence: A key virulence study.

Bacterial adhesion is a threshold event in the formation of biofilms which leads to serious bacterial diseases. This shows that the underlining the problem is interesting and need to solve the problem of biofilm-related complications. To support this, in the present study, we first time initiated to understand the role of methicillin-resistant Staphylococcus aureus (MRSA) biofilm using previously developed benzodioxane midst piperazine decorated chitosan silver nanoparticles (BP*C@AgNPs). The BP*C@AgNPs studied for antimicrobial, anti-biofilm, biofilm adherence inhibition, the role of ions in biofilm, and an antibiotic cocktail in the treatment of biofilm was assessed. The results showed that, the significant biocidal role of BP*C@AgNPs in controlling the MRSA biofilm and interaction of biofilm protein to calcium ions were significantly decreased. This confirms that calcium ion involved in the biofilm formation and for the treatment of BP*C@AgNPs, cocktail of enzyme and antibiotic have the promising therapeutic value was observed. In future the locking of biofilm protein and its expression in presence of calcium ion was interesting, and greater application related to biofilm infection was warrantable.

Ectopic Bone as a Nidus for Calcium Oxalate Urocystolithiasis in a Cat.

A 7-year-old female spayed domestic shorthair cat was referred to the urology service for nonsurgical urocystolith removal. A urolith was attached to the urothelium by ectopic bone. Interventional removal without surgery was successful. Follow-up evaluation 3 years after urolith removal revealed recurrent uroliths, bladder wall mineralization, and marked renal mineralization. This case illustrates the metaplastic potential of the urothelium and that ectopic bone should be included among the pathological factors that promote lithogenesis.

A histologic assessment of a HYBENX® oral tissue decontaminant in vital pulp therapy in dogs.

The aim of this study was to assess HYBENX® Oral Tissue Decontaminant (HOTD) in treating vital pulp exposure in a canine model. The use of HOTD solution was compared to an accepted and standard regimen for vital pulp exposure, an application of a commercial calcium hydroxide product (Ca(OH)2). Both control and experimental treatments were followed by restoration with a commercial zinc oxide and eugenol obtundant intermediate restorative material and thermal insulator (ZOE). At 7 days there was 100% pulp vitality with HOTD and 50% with Ca(OH)2. New dentin formation was seen in 62.5% of the HOTD treated pulps and none of the Ca(OH)2 treatment group. The vital pulp exposures at day 21 post treatment with HOTD also showed significant improvement over Ca(OH)2 in the presence of odontoblasts, new dentin formation and pulp survivability. The presence of odontoblasts and new dentin was noted in 71% of the HOTD cases versus 50% of the survivable Ca(OH)2 cases. Furthermore, 100% of HOTD cases had vital pulps versus 62.5% of Ca(OH)2 cases. The 60-day specimens of both experimental and control techniques exhibited histologically similar appearances and were similar in outcomes. HOTD treatment at day 7 showed a significant positive difference, both in the formation of new dentin and tooth vitality. HOTD proved better for the post 21-day specimens and equivalent for the 60-day pulp specimens with no evidence of untoward tissue reactions or results.

Potential effects of tetrodotoxin exposure to human glial cells postulated using microarray approach.

Sodium channels play an important role in many neurological disorders and also in prostate cancer. Tetrodotoxin (TTX), a blocker of voltage-gated sodium channels has been chiefly used as a molecular probe for the study and characterization of these channels. The regulation of gene expression in response for the exposure of TTX to glial cells which are reported to be involved in neurodegenerative process is poorly understood. Therefore, the present study aims to develop a repository of genes and map it on a few pivotal neurodegenerative pathways to speculate the effect of TTX. Using Affymetrix GeneChip (HG-U133A), we have selected a subset of 692 differentially expressed genes, several of which are-cullin 4A (CUL4A), ubiquitin carrier protein (E2-EPF), proteasome (prosome, macropain) subunit, beta type, 8 (large multifunctional protease 7) (PSMB8), protein tyrosine phosphatase type IVA (PTP4A1), intercellular adhesion molecule 1 (ICAM1), prostaglandin-endoperoxide synthase 2 (PTGS2), and caspase 1 (CASP1). These genes, which facilitate some of the neurodegenerative pathways, such as ubiquitin, proteasome, inflammation and kinases, were identified to be up- or down-regulated for the TTX treatment. Thus, the selected genes were further examined on ubiquitin-proteasome mediated inflammatory responses pathway as ample evidence for the role of glial cell-mediated inflammation in the neurodegenerative process are available. In summary, our result provides a basic understanding of the differentially expressed genes along with one of the possible pathway which may have been modulated by the exposure of TTX.

Design, synthesis and antibacterial activity studies of model peptidess of proline/arginine-rich region in bactenecin7.

Bactenecin 7 (Bac7), a cationic antibacterial peptide, contains a repeating region of Xaa-Pro-Arg-Pro (Xaa = hydrophobic residue). To investigate the structure and property of a Pro/Arg-rich region, e synthesized a series of peptides, Xaa-Pro-Arg-Pro (Xaa = Gly, Arg, Leu, Ile, and Phe) as models and characterized . The conformational preferences of these peptides in water and trifluoroethanol were examined by circular dichroism. The results suggest the presence of largely poly(Pro)-II helical conformation in aqueous and trifluoroethanol solutions. Their antibacterial activity against gram-negative bacteria such as Escherichia coli, Klebsiella Pneumoniae, Pseudomonas aeruginosa, and Escherichia coliHB101, and gram-positive bacteria such as Staphylococcus aureus were measured at various peptide concentrations. Two of our synthetic tetrapeptide fragments containing Gly and Arg were efficiently killed with gram-positive bacteria, Staphylococcus aureus, at the concentration level of 200 microg/mL.

Frequency of stromal lineage colony forming units in bone marrow of peroxisome proliferator-activated receptor-alpha-null mice.

The bone marrow stroma, consisting of adipocytes, fibroblasts, and osteoblasts, develops from a multipotent mesenchymal progenitor. The recently described nuclear hormone receptors, known as peroxisome proliferator-activated receptors (PPARs), regulate transcription of genes involved in adipogenesis. Consistent with this is the observation that PPARalpha-null mice exhibit greater extramedullary adipose stores compared with their wild-type controls. To determine if the status of the PPARalpha protein also influenced bone marrow stromal cell differentiation, this study compared the frequency of colony forming units for bone marrow adipocytes (CFU-A), alkaline phosphatase-positive fibroblasts (CFU-F/ALP+), and osteoblasts (CFU-O) between wild-type and PPARalpha-null mice. The CFU frequencies for all lineages were not significantly different in either gender at age 3 weeks, independent of the PPARalpha background. However, histologic analysis showed that the cross-sectional area of the femur in male PPARalpha null mice was significantly greater than that of PPARalpha-null female mice and of both wild-type genders. This was due to an increased marrow cavity space rather than an increased cortical bone area. In addition, while the percentage area of cortical bone occupied by lacunae was equivalent in the PPARalpha and wild-type males, this value was significantly greater in PPARalpha-null female mice compared with wild-type females. At age 3-6 months, no significant difference was observed in the CFU-A frequencies, based on either PPARalpha status or gender. The wild-type male CFU-F/ALP+ frequency was significantly greater than the CFU-F/ALP+ in all other groups. Although the PPARalpha status had no influence on the CFU-O frequency, the number of CFU-O was greater in male than in female mice. Sequential incubation of stromal cells in either adipogenic- or osteoblastic-inducing media did not alter the number of CFU-A or CFU-O. These results indicate that the PPARalpha-null genotype does not influence bone marrow stromal cell numbers.

Tendon-to-bone healing of a semitendinosus tendon autograft used for ACL reconstruction in a sheep model.

Anterior cruciate ligament (ACL) reconstruction was performed in a single hind limb of 30 sheep using a doubled semitendinosus tendon graft. Three additional animals were used as controls. Histologic and biomechanical analysis was performed from 4-52 weeks postoperatively. Perpendicular collagen fibers were found connecting the tendon graft to the bone tunnels at 8 weeks. These fibers were seen circumferentially at 12 weeks. By 24 weeks, the bone tunnel was well-defined, and no further changes were observed at 52 weeks. Tendon incorporation within the femoral and tibial tunnels was similar at each interval. Although the small sample size did not permit statistical testing, the reconstruction strength was similar up to 12 weeks (15%-19% of controls). This increased at 24 (28%) and 52 (40%) weeks. The stiffness primarily increased from 4-8 weeks (18%-39%) and 24-52 weeks (52%-82%). Up to 12 weeks, failures occurred by graft pull-out from the bone tunnel. All 24- and 52-week specimens ruptured through the intra-articular portion of the graft, further indicating sufficient graft incorporation within the bone tunnels.

Postmortem histologic evaluation of mandibular titanium and maxillary hydroxyapatite-coated implants from 1 patient.

Postmortem examination of human specimens is an extremely important aspect of evaluating the relative compatibility and long-term success of endosseous implant surfaces. The bone-implant interface of 5 commercially pure titanium screw-type mandibular implants after 85 months of service and 2 hydroxyapatite- (HA) coated maxillary implants after 38 months of service were examined. All implants were stable at the time of the patient's death. The mandibular implants had an average of 65% contact with bone and the maxillary implants had an average of 47% contact. The HA coating had separated from the maxillary implants in some areas and was free within surrounding connective tissue or surrounded by invaginating sulcular epithelium. The arrangement and pattern of bone contact appeared different between HA-coated and titanium implant surfaces.

Rectal adenocarcinoma in an HIV-infected haemophiliac: case report and review.

Colorectal adenocarcinoma, a relatively uncommon malignancy associated with HIV infection, is now being increasingly recognized. Most reports have been in homosexuals and intravenous drug users and there are no reports of its occurrence in haemophiliacs acquiring HIV via infused factor VIII and without other obvious risk factors or a family history. The present report describes the case of a young heterosexual haemophiliac with HIV infection and no other risk factors who developed rectal carcinoma. The relevant literature is discussed and the clinical importance of recognizing this possible association is emphasized.

Circulating inhibitor associated with viral infection.

A 12-year-old boy presented with bleeding and fever. He was found to have developed an inhibitor to factors VIII and IX, probably associated with a viral infection.