Genetic Cell Therapy in Anti-Aging Regenerative Cosmetology

As post-WWII baby boomer approaching age 80, Anti-Aging Regenerative Cosmetology (AARC) has been developed and patented for beautifying and strengthening the human body using live cells;to enhance the appearance and function of various bodily parts to provide health and aestheticism of human being throughout life. It is a combined cosmetic and preventive medicine to intervene with and to correct the undesirable phenotypic expression of aging. The intrinsic properties of myoblasts and foreskin fibroblasts in development and regeneration are harnessed to formulate a genetic cell therapy program which is safe and efficacious as previously been tested in FDA Phase III clinical trials. Myoblasts are selected for strength development and foreskin fibroblasts for tenacity and smooth-to-the-touch. Both cell types are highly mitotic and non-carcinogenic. In additional to providing large quantities of nuclei as regenerative gene medicine, and of mitochondria as energy generators, myoblasts secret tumor necrosis factor alpha (TNF-α) for skin whitening and melanoma prevention. Myoblasts, because of their small size, spindle shape, and resilience, grow readily on collagen and laminin within wrinkles of skin surfaces, thus enhancing the color, luster, and texture of the skin “plated” with them. Alternatively, they can be injected subcutaneously as cell filler to reduce wrinkles. Intramuscular injection of myoblasts can augment the size, shape, consistency, tone, and strength of muscle groups, improving the lines, contours, and vitality to sculpt a youthful appearance. By improving cell genetics and organ functions, the program holds promise to sustain the human subject in good health and appearance, with a good quality of life and life prolongation.

Menstrual Abnormalities and Gynaecological Problems in Women on Anticoagulant and Antiplatelet Therapy: Management Options

Introduction: The aim of this study was: 1) To study the pattern of menstrual abnormality and severity in women on anticoagulant and antiplatelet drugs. 2) To analyze the correlation of prothrombin time (PT), International Normalised ratio (INR) and the bleeding severity. 3) To discuss the various management options in unexpected emergencies and menstrual complications in this subset of women on anticoagulants. Material & Methods: It is a prospective study, over a period of 18 months from July 2011 to december 2012. We had 44 women on antithrombotic therapy. 32 women were on anticoagulants and 12 were on antiplatelet agents. The severity of bleeding pattern was assessed with pictoral bleeding assessment chart (PBAC). 1) Out of 44 women studied, 32 women were on anticoagulants and 12 were on antiplatelet agents. 26 (81.25%) were on acenocoumarol, 5 (15.62%) on warfarin, 1 (3.12%) on heparin, among the 12 antiplatelet users, 8 (66.66%) were on aspirin and 4 (33.33%) on clopidogrel. 2) The indication for anticoagulants was mitral valve replacement (MVR) in 9, double valve replacement (DVR) in 6, aortic valve replacement (AVR) in 3, severe pulmonary artery hypertension (PAH) in 2, severe mitral stenosis (MS) with atrial thrombus in 2, deep vein thrombosis (DVT) in 5, severe mitral regurgitation (MR) in one, the other indications were subdural hematoma, thromboendarterectomy, chronic kidney disease (CKD) stage V, coarction of aorta, one each. The indication for antiplatelet therapy was percutaneous transluminal coronary angioplasty (PTCA) in 3, Wolf Parkinson White (WPW) syndrome + atrial fibrillation (AF), acute myocardial infarction (AMI), coronary artery bypass graft (CABG), mid basilar artery aneurysm, renal allograft recipient, dialated cardiomyopathy, aortic aneurysm repair, hypertension and unstable angina one each. Results: In women on anticoagulants (32), the main complaint was menorrhagia/heavy menstrual bleeding (HMB) in 20, polymenorrhoea with menorrhagia in 4, continuous per vaginal (PV) bleeding in 6. One lady had postmenopausal bleeding. Among the 12 antiplatelet users the main complaint was menorrhagia in 8, polymenorrhoea with menorrhagia in 2, postmenopausal bleeding in one. While on antithrombotic therapy apart from heavy menstrual bleeding, two women had intraperitoneal bleeding, two had post menopausal bleeding, two had secondary postpartum bleeding (PPH). CVA due to embolic stroke occurred in three, one during the study period. Subchoroidal haemorrhage causing choroidal detachment was noted in one. Conclusions: In patients with prolonged INR, excessive uterine bleeding can be an alerting initial manifestation. Antithrombotic therapy can cause HMB or exaggerate the symptom of HMB due to an underlying gynaec pathology. Mefanamic acid and norethisterone were used to arrest heavy menstrual bleeding. Antithrombotic therapy in women needs special consideration with alterations in menstrual pattern and contraception. Pregnancy and postpartum period present special challenges.

A new look at anti-Helicobacter pylori therapy

With the rising prevalence of antimicrobial resistance,the treatment success of standard triple therapy has recently declined to unacceptable levels (i.e.,80% or less) in most countries.Therefore,several treatment regimens have emerged to cure Helicobacter pylori (H.pylori) infection.Novel first-line anti-H.pylori therapies in 2011 include sequential therapy,concomitant quadruple therapy,hybrid (dual-concomitant) therapy and bismuth-containing quadruple therapy.After the failure of standard triple therapy,a bismuth-containing quadruple therapy comprising a proton pump inhibitor (PPI),bismuth,tetracycline and metronidazole can be employed as rescue treatment.Recently,triple therapy combining a PPI,levofloxacin and amoxicillin has been proposed as an alternative to the standard rescue therapy.This salvage regimen can achieve a higher eradication rate than bismuth-containing quadruple therapy in some regions and has less adverse effects.The best second-line therapy for patients who fail to eradicate H.pylori with first-line therapies containing clarithromycin,amoxicillin and metronidazole is unclear.However,a levofloxacin-based triple therapy is an accepted rescue treatment.Most guidelines suggest that patients requiring third-line therapy should be referred to a medical center and treated according to the antibiotic susceptibility test.Nonetheless,an empirical therapy (such as levofloxacin-based or furazolidone-based therapies) can be employed to terminate H.pylori infection if antimicrobial sensitivity data are unavailable.

Anti-Helicobacter pylori therapy significantly reduces Helicobacter py/ori-Induced gastric mucosal damage in Mongolian gerbils

AIM: To investigate the effectiveness of 4 d' anti-Helicobacter pyloritherapy on the H pylori-infected Mongolian gerbils based on physiological and pathological changes.METHODS: We used 6-wk-old male gerbils orally inoculated with H pylori (ATCC43504, 2x108 CFU/mL).Seven weeks after H pylori inoculation, the animals of study group received 4 d' anti-H pylori triple therapy (H pylorieradicated group). Seven days later, all animals of the H pylori-eradicated and control groups (H pylori-infected& H pylori-uninfected groups) were sacrificed. We examined gastric mucosal lesions macroscopically, studied gastritis microscopically and determined the stomach weight ratio, myeloperoxidase (MPO) activity and prostaglandin (PG) E2 level.RESULTS: The results showed that both macroscopic and histological gastric damages were significantly less in H pylori-eradicated group than H pylori-infected group.Stomach weight ratio, MPO activity and PGE2 levels were significantly higher in H pylori-infected group than those in the other two groups.CONCLUSION: Four days' anti-H pylori therapy was effective in the improvement of H pylori-induced gastric lesions in Mongolian gerbils.

Exploration and Study of Jianpi Qushi Powder Combined with Standard Anti HP Quadruple Therapy in the Treatment of HP Infectious Gastritis of Spleen Deficiency and Dampness Stagnation Type

Objective: To explore the therapeutic effect of traditional Chinese medicine Jianpi Qushi powder combined with standard anti-HP quadruple therapy in the treatment of HP infectious gastritis with spleen deficiency and dampness stagnation. Methods: From January 2020 to December 2021, 223 patients with laboratory-confirmed HP infection who were admitted to the Outpatient and Inpatient Department of Internal Medicine in our hospital were selected as the research objects and randomly divided into two groups. 101 patients in the control group were given standard anti HP quadruple therapy;122 cases in the treatment group were given traditional Chinese medicine Jianpi Qushi powder combined with standard anti HP quadruple therapy. The two groups were rechecked carbon breath test after the designed course of treatment, and the curative effects of the two groups were compared. Results: 113 cases in the treatment group were cured by traditional Chinese medicine Jianpi Qushi powder combined with standard anti HP quadruple therapy, and the cure rate was 92.62%. 84 cases in the control group were cured by standard anti HP quadruple therapy, and the cure rate was 83.17%, χ2 = 4.7955, P = 0.0285, the difference was statistically significant (P < 0.05). Conclusion: Traditional Chinese medicine Jianpi Qushi powder combined with standard anti HP quadruple therapy in the treatment of HP infectious gastritis with spleen deficiency and dampness stagnation is one of the best treatment schemes for HP infection. The results of this study achieve the best clinical treatment effect, and provide a more valuable and reliable method for the treatment of gastropathy in clinical internal medicine, which is worthy of popularization and application.

Role of anti-angiogenesis therapy in the management of hepatocellular carcinoma: The jury is still out

As the leading cause of disease-related deaths,cancer is a major public health threat worldwide.Surgical resection is still the first-line therapy for patients with early-stage cancers.However,postoperative relapse and metastasis remain the cause of 90%of deaths of patients with solid organ malignancies,including hepatocellular carcinoma(HCC).With the rapid development of molecular biology techniques in recent years,molecularly targeted therapies using monoclonal antibodies,small molecules,and vaccines have become a milestone in cancer therapeutic by significantly improv-ing the survival of cancer patients,and have opened a window of hope for patients with advanced cancer.Hypervascularization is a major characteristic of HCC.It has been reported that anti-angiogenic treatments,which inhibit blood vessel formation,are highly effective for treating HCC.However,the efficacy and safety of anti-angiogenesis therapies remain controversial.Sorafenib is an oral multikinase inhibitor with antiproliferative and anti-angiogenic effects and is the first molecular target drug approved for the treatment of advanced HCC.While sorafenib has shown promising therapeutic effects,substantial evidence of primary and acquired resistance to sorafenib has been reported.Numerous clinical trials have been conducted to evaluate a large number of molecularly targeted drugs for treating HCC,but most drugs exhibited less efficacy and/or higher toxicity compared to sorafenib.Therefore,understanding the mechanism(s)underlying sorafenib resistance of cancer cells is highlighted for efficiently treating HCC.This concise review aims to provide an overview of anti-angiogenesis therapy in the management of HCC and to discuss the common mechanisms of resistance to anti-angiogenesis therapies.

Hepatitis C: From inflammatory pathogenesis to antiinflammatory/hepatoprotective therapy

Hepatitis C virus(HCV) infection commonly causes progressive liver diseases that deteriorate from chronic inflammation to fibrosis, cirrhosis and even to hepatocellular carcinoma. A long-term, persistent and uncontrolled inflammatory response is a hallmark of these diseases and further leads to hepatic injury and more severe disease progression. The levels of inflammatory cytokines and chemokines change with the states of infection and treatment, and therefore, they may serve as candidate biomarkers for disease progression and therapeutic effects. The mechanisms of HCV-induced inflammation involve classic pathogen pattern recognition, inflammasome activation, intrahepatic inflammatory cascade response, and oxidative and endoplasmic reticulum stress. Direct-acting antivirals(DAAs) are the first-choice therapy for effectively eliminating HCV, but DAAs alone are not sufficient to block the uncontrolled inflammation and severe liver injury in HCV-infected individuals. Some patients who achieve a sustained virologic response after DAA therapy are still at a long-term risk for progression to liver cirrhosis and hepatocellular carcinoma. Therefore, coupling with antiinflammatory/hepatoprotective agents with anti-HCV effects is a promising therapeutic regimen for these patients during or after treatment with DAAs. In this review, we discuss the relationship between inflammatory mediators and HCV infection, summarize the mechanismsof HCV-induced inflammation, and describe the potential roles of anti-inflammatory/hepatoprotective drugs with anti-HCV activity in the treatment of advanced HCV infection.

Pancreatic tuberculosis mimicking pancreatic carcinoma during anti-tuberculosis therapy:A case report

Pancreatic tuberculosis(TB) is a rare condition,even in immunocompetent hosts.A case is presented of pancreatic TB that mimicked pancreatic head carcinoma in a 40-year-old immunocompetent male patient.The patient was admitted to our hospital after suffering for nine days from epigastralgia and obstructive jaundice.Computed tomography revealed a pancreatic mass that mimicked a pancreatic head carcinoma.The patient had undergone an operation four months prior for thoracic TB and was undergoing anti-TB therapy.A previous abdominal ultrasound was unremarkable with the exception of gallbladder steroid deposits.The patient underwent surgery due to the progressive discomfort of the upper abdomen and a mass that resembled a pancreatic malignancy.A biopsy of the pancreas and lymph nodes was performed,revealing TB infection.The patient received a cholecystostomy tube and recovered after being administered standard anti-TB therapy for 15 mo.This case is reported to emphasize the rarecontribution of pancreatic TB to pancreatic masses and obstructive jaundice.

Tumor budding predicts response to anti-EGFR therapies in metastatic colorectal cancer patients

AIM:To investigate whether the evaluation of tumor budding can complement K-RAS analysis to improve the individualized prediction of response to anti-epidermal growth factor receptor based therapies in metastatic colorectal cancer (mCRC) patients. METHODS:Forty-three patients with mCRC treated with cetuximab or panitumumab were entered into this study. According to the Response Evaluation Criteria in Solid Tumors criteria, 30 patients had stable or progressive disease (non-responsive), while 13 patients had a partial response. Tumor buds were evaluated from whole tissue sections stained for pan-cytokeratin, evaluated in the densest region using a 40 × objective and "high-grade" tumor budding was defi ned as 15 buds/high-power f ield.RESULTS: Tumor buds and K-RAS mutation both correctly classif ied 68% of patients. All patients with K-RAS mutation (n=7) or high-grade tumor budding (n=11) were non-responsive, of which 4 patients had both features. All 13 partial responders were K-RAS wild-type with low-grade tumor budding. Combined, the predictive value of K-RAS and tumor budding was 80%. Additionally, high-grade tumor budding was significantly related to worse progression-free survival [HR (95% CI): 2.8 (1.3-6.0, P=0.008)].CONCLUSION: If confirmed in larger cohorts, the addition of tumor budding to K-RAS analysis may represent an effective approach for individualized patient management in the metastatic setting.

An eighteen-month follow-up study on the effects of Intravitreal Dexamethasone Implant in diabetic macular edema refractory to anti-VEGF therapy

AIM： To evaluate the long-term efficacy and safety of dexamethasone implants in subjects affected by diabetic macular edema（DME） resistant to anti-vascular endothelial growth factor（VEGF） therapy.METHODS： Thirty-two DME patients were enrolled.A700 microgram slow release Intravitreal Dexamethasone Implant（Ozurdex~） was placed in the vitreous cavity.All patients were followed for 18 mo.Best-corrected visual acuity（BCVA） measured with Early Treatment Diabetic Retinopathy Study（ETDRS） and central macular thickness（CMT） exams were carried out at baseline（T0）and after 1（T1）,3（T3）,4（T4）,6（T6）,9（T9）,12（T12）,15（T15）,and 18mo（T18） post injection. RESULTS： Repeated measures ANOVA showed an effect of treatment on ETDRS（P〈0.0001）.Post hoc analyses revealed that ETDRS values were significantly increased at T1,T3,T4,T9,and T15（P 〈0.001） as compared to baseline value（T0）.At T6,T12,and T18,ETDRS values were still statistically higher than baseline（P〈0.001 vs T0）.However,at these time points,we observed a trend to return to baseline conditions.ANOVA also showed an effect of treatment（P 〈0.0001）.CMT decreased significantly at T1,T3,T4,T9,and T15（P〈0.001）.At T6（P〈0.01）,T12 and T18（P〈0.001） CMT was also significantly lower than T0 although a trend to return to the baseline conditions was also observed.CONCLUSION： Our findings demonstrate that Intravitreal Dexamethasone Implant is a good option to improveBCVA and CMT in DME patients resistant to anti-VEGF therapy.Our data also show that the use of drugs administered directly into the vitreous allows achieving appropriate and long-lasting concentration at the site of disease without systemic side effects.

Withdrawal of anti-tumour necrosis factor α therapy in inflammatory bowel disease

Anti-tumour necrosis factor α(anti-TNFα) therapy is an established treatment in inflammatory bowel disease.However, this treatment is associated with high costs and the possibility of severe adverse events representing a true challenge for patients, clinicians and health care systems.Consequently, a crucial question is raised namely if therapy can be stopped once remission is achieved and if so, how and in whom.Additionally, in a real-life clinical setting, discontinuation may also be considered for other reasons such as the patient's preference, pregnancy, social reasons as moving to countries or continents with less access, or different local policy or reimbursement.In contrast to initiation of anti-TNFα therapy guidelines regarding stopping of this treatment are missing.As a result, the decision of discontinuation is still a challenging aspect in the use of anti-TNFα therapy.Currently this is typically based on an estimated, case-by-case, benefit-risk ratio.This editorial is intended to provide an overview of recent data on this topic and shed light on the proposed drug withdrawal strategies.

Prognostic and predictive biomarkers in metastatic colorectal cancer anti-EGFR therapy

AIM: To reviewing genetic and epigenetic make-up of metastatic colorectal cancers(m CRCs) addicted to epidermal growth factor receptor(EGFR) signalling.METHODS: The present study summarizes the potential value of prognostic and predictive biomarkers in selecting m CRC patients treated with anti-EGFR therapy. A meta-analysis was performed using a systematic search of Pub Med, Medline and Web of Science to identify eligible papers until March 21 st, 2016 using these following terms: ‘‘colorectal cancer'', "predictive biomarkers' ', "anti-EGFR therapy", "KRAS", "NRAS'', "PIK3CA", "TP53", "PTEN", ‘‘EGFR", "MET", "HER2", "epiregulin", "amphiregulin", "prognostic biomarkers", "BRAF", "miR NA" and "antibody-dependent cell-mediated cytotoxicity(ADCC) activity". Two investigators independently evaluated and extracted data from each identified studies based on selected criteria of inclusion and exclusion. RESULTS: The introduction of agents targeting EGFR such as cetuximab and panitumumab increased overall survival of mC RCs. Nevertheless, it has firstly became evident that response rates to cetuximab regimens in unselected patient populations were typically lower than 30%. Clinical data confirmed the predictive value of RAS mutations for resistance to cetuximab and panitumumab leading to the license of these monoclonal antibodies exclusively for the management of patients with RAS-wild type colorectal cancers. So far the identification of predictive biomarkers have generated interesting, though preliminary and, at times, conflicting data on the importance of tumour mR NA levels of EGFR ligands, of activating mutations in other genes such as NRAS and PIK3 CA. The prognostic value of selected micro RNAs level and ADCC activity is under investigation, while the prognostic impact of BRAF status remains controversial.CONCLUSION: This review focuses on the personalized treatment of m CRC and discusses the potential of new prognostic and predictive biomarkers in selecting patients treated with anti-EGFR therapy.

Role of Anti Angiogenic Therapy in Prevention of Recurrence in Hormonal Positive Breast Cancer: A Secondary Prevention Strategy and Method of Therapy

Existing literature supports the role of signaling protein vascular endothelial growth factor (VEGF) in tumor growth and metastasis and furthers its involvement in recurrence. In both experimental and clinical studies, VEGF has been shown to be a significant factor involved for aberrant blood vessel growth, and in fact is the target of several classes of antineoplastic drugs [1] [2] [3] [4]. That said, the current standard of care for estrogen receptor positive breast cancer (although improved over the last decade), has not provided a “meaningful preventive shift” since the discovery of angiogenesis and its role in induction of recurrence. In this article, we discuss an anti angiogenic therapy implementing natural compounds to inhibit the production of VEGF. We applied our preclinical data to justify the predicted effect on VEGF. We used liquid biopsy to monitor patients response to therapy as a surrogate for recurrence. We hypothesize that by inhibition of angiogenesis through this protocol, we are able to positively impact tumor recurrence. It is our experience that patients in our sample even with high recurrence scores (based on Oncotype Dx testing) had a major reduction in recurrence when estrogen blockers were combined with this protocol. We also propose longitudinal studies to compare outcomes with combinational therapies with estrogen blockers in highly expected to recur disease.

Changing common sense:Anti-platelet/coagulation therapy against cirrhosis

Until recently,anti-platelet/coagulation therapy had not been recommended for patients with cirrhosis.Although venous thrombosis is one of the representative complications of cirrhosis and ischemic disorders associated with atherosclerosis are not infrequent in cirrhotic patients,many clinicians have tended to hesitate to introduce anti-platelet/coagulation therapy to their patients.Undoubtedly,this is due to the increased risk of hemorrhagic diathesis in cirrhotic patients.However,accumulating evidence has revealed the benefits of anti-platelet/coagulation therapy for cirrhotic patients.In addition to the safety of the therapy carried out against cardiovascular diseases in cirrhotic patients,some clinical data have indicated its preventive effect on venous thrombosis.Moreover,the efficacy of antiplatelet/coagulation therapy against cirrhosis itself has been demonstrated both clinically and experimentally.The conceptual basis for application of anti-platelet/coagulation therapy against cirrhosis was constructed through two pathologic studies on intrahepatic thrombosis in cirrhotic livers.It may be better to use thrombopoietinreceptor agonists,which have been tested as a treatment for cirrhosis-related thrombocytopenia,in combination with anti-platelet drugs to reduce the risk of venous thrombosis.During the last decade,the World Journal of Gastroenterology,a sister journal of World Journal of Hepatology,has been one of the main platforms of active discussion of this theme.

Immune response after photodynamic therapy increases anti-cancer and anti-bacterial effects

Photodynamic therapy(PDT) is a clinically approved procedure for treatment of cancer and infections. PDT involves systemic or topical administration of a photosensitizer(PS), followed by irradiation of the diseased area with light of a wavelength corresponding to an absorbance band of the PS. In the presence of oxygen, a photochemical reaction is initiated, leading to the generation of reactive oxygen species and cell death. Besides causing direct cytotoxic effects on illuminated tumor cells, PDT is known to cause damage to the tumor vasculature and induce the release of pro-inflammatory molecules. Pre-clinical and clinical studies have demonstrated that PDT is capable of affecting both the innate and adaptive arms of the immune system. Immune stimulatory properties of PDT may increase its beneficial effects giving the therapy wider potential to become more extensively used in clinical practice. Be-sides stimulating tumor-specific cytotoxic T-cells capable to destroy distant untreated tumor cells, PDT leads to development of anti-tumor memory immunity that can potentially prevent the recurrence of cancer. The immunological effects of PDT make the therapy more effective also when used for treatment of bacterial infections, due to an augmented infiltration of neutrophils into the infected regions that seems to potentiate the outcome of the treatment.

Numerical simulation of inhibiting effects on solid tumour cells in anti-angiogenic therapy: application of coupled mathematical model of angiogenesis with tumour growth

To investigate the inhibiting effects of the anti-angiogenic factor andostatin and the anti-angiogenic drug endostatin on turnout angiogenesis and turnout cells, a coupled mathematical model of tumor angiogenesis with tumour growth and blood perfusion is developed. Simulation results show that angiostatin and endostatin can improve the abnormal microenvironment inside the tumour tissue by effectively inhibiting the process of tumor angiogenesis and decreasing tumour cells. The present model can be used as a valid theoretical method in the investigation of the tumour anti-angiogenic therapy.

Potent antiviral therapy improves survival in acute on chronic liver failure due to hepatitis B virus reactivation

Acute on chronic liver failure(ACLF)is a disease entity with a high mortality rate.The acute event arises from drugs and toxins,viral infections,bacterial sepsis,interventions(both surgical and non-surgical)and vascular events on top of a known or occult chronic liver disease.ACLF secondary to reactivation of chronic hepatitis B virus is a distinct condition;the high mortality of which can be managed in the wake of new potent antiviral therapy.For example,lamivudine and entecavir use has shown definite short-term survival benefits,even though drug resistance is a concern in the former.The renoprotective effects of telbivudine have been shown in a few studies to be useful in the presence of renal dysfunction.Monotherapy with newer agents such as tenofovir and a combination of nucleos(t)ides is promising for improving survival in this special group of liver disease patients.This review describes the current status of potent antiviral therapy in patient with acute on chronic liver failure due to reactivation of chronic hepatitis B,thereby providing an algorithm in management of such patients.

Recovery rates of combination antibiotic therapy using in vitro microdialysis simulating in vivo conditions

Microdialysis is a technique used to measure the unbound antibiotic concentration in the interstitial spaces, the target site of action. In vitro recovery studies are essential to calibrating the microdialysis system for in vivo studies. The effect of a combination of antibiotics on recovery into microdialysate requires investigation. In vitro microdialysis recovery studies were conducted on a combination of vancomycin and tobramycin, in a simulated in vivo model. Comparison was made between recoveries for three different concentrations and three different perfusate flow rates. The overall relative recovery for vancomycin was lower than that of tobramycin. For tobramycin, a concentration of 20μg/mL and flow rate of 1.0μL/min had the best recovery. A concentration of 5.0μg/mL and flow rate of 1.0μL/min yielded maximal recovery for vancomycin. Large molecular size and higher protein binding resulted in lower relative recoveries for vancomycin. Perfusate flow rates and drug concentrations affected the relative recovery when a combination of vancomycin and tobramycin was tested. Low perfusate flow rates were associated with higher recovery rates. For combination antibiotic measurement which includes agents that are highly protein bound, in vitro studies performed prior to in vivo studies may ensure the reliable measurement of unbound concentrations.

Hemolysins of <i>Staphylococcus aureus</i>—An Update on Their Biology, Role in Pathogenesis and as Targets for Anti-Virulence Therapy

Staphylococcus aureus is a dangerous gram positive bacterial pathogen which, not only evades the host’s immune system but also can destroy the leucocytes especially neutrophils. It has an embodiment of virulence factors most of which are secreted. Staphylococcus aureus secretes a number of toxins which cause tissue damage and facilitate spreading and nutrients uptake. Among the toxins, hemolysins α, β, γ, δ and Panton Valentine Leukocidin (PVL) are unique that they drill pores in the membrane, leading to the efflux of vital molecules and metabolites. Hemolysins also help in the scavenging of iron, although many of them also have leucolytic properties. α-hemolysin, also known as α-toxin, is the most prominent cytotoxin which damages a wide range of host cells including epithelial cells, endothelial cells, erythrocytes, monocytes, keratinocytes and it damages cell membrane and induces apoptosis. β-Hemolysin significantly affects human immune cell function. It has Mg2+ dependent sphingomyelinase activity and degrades sphingomyelin of plasma membrane into phosphorylcholine and ceramides. The bi-component leukocidins, which include γ-hemolysin and PVL, attack human phagocytic cells and greatly contribute to immune evasion. Delta toxin is a low molecular weight exotoxin with a broad cytolytic activity. Virulence determinants, quorum sensing and biofilm synthesis provide some attractive targets for design and development of a new group of antimicrobial compounds. This review provides an update on the structure, biological functions of hemolysins and their role in quorum sensing/biofilm synthesis (if any) and as effective therapeutic targets for anti-virulence drug development. We have tried to bring together information available on various aspects of hemolysins and highlighted their distribution among all species of Staphylococcus and other bacteria. We have updated the status of development of candidate drugs targeting the hemolysins for anti-virulence therapy as it offers an additional strategy to reduce the severity of infection and which would, through quorum quenching, delay the development biofilms leading to drug resistance.

Anti-CD-20 Therapy in Refractory Adult Still’s Disease

Adult Still’s disease is a relatively rare form of rheumatoid arthritis with systemic inflammatory features. The prevalence is around 1.5 cases per 100,000 - 1000,000. In the current case we display a 30-year-old male patient with refractory adult still’s disease who suffered recurrent attacks of fever 39.5°C, arthritis in proximal interphalangeal joints (PIPs), wrists, tempromandibular joints (TMJs), knees and ankles, stitching chest pain, dyspnea, erythematous rash over the trunk, sore throat, weight loss (15 Kilograms in 4 months). The patients’ disease remained uncontrolled despite of synthetic disease modifying anti-rheumatic drugs and repeated intramuscular corticosteroid injections. Laboratory workup revealed erythrocyte sedimentation rate (ESR) of 95, C-reactive protein (CRP) of 100 mg/L, hemoglobin 10.5 gm%, leukocytosis 12,000/microlitre, mild elevation of liver function tests and dyslipidemia. Serology revealed negative rheumatoid factor, anti-nuclear antibody titre of 1:80, elevated serum ferritin 4000 micrograms/litre. The patient was started on rituximab (375 mg/m2), prednisolone 20 mg/day and selective Cox-2 inhibitor. Follow up for over three months following the completion of his pulse therapy, revealed no relapse of fever or fatigue, with morning stiffness of 5 - 10 minutes, VAS of 3, DAS28 of 3.8, HAQDI of 0.62, ESR 23, CRP 4.9, Hb 12.5 gm%, leucocytic count 9000/microlitre, the dose of prednisolone was successfully reduced to a dose of 5 mg/day orally. Conclusion: Anti-CD20 therapy successfully controlled systemic and articular refractory disease with sustained efficacy over a follow up period of up to 24 weeks.