Immune-related therapeutics: an update on antiviral drugs and vaccines to tackle the COVID-19 pandemic

The coronavirus disease 2019 (COVID-19) pandemic rapidly spread globally. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, is a positive-sense single-stranded RNA virus with a reported fatality rate ranging from 1% to 7%, and people with immune-compromised conditions, children, and older adults are particularly vulnerable. Respiratory failure and cytokine storm-induced multiple organ failure are the major causes of death. This article highlights the innate and adaptive immune mechanisms of host cells activated in response to SARS-CoV-2 infection and possible therapeutic approaches against COVID-19. Some potential drugs proven to be effective for other viral diseases are under clinical trials now for use against COVID-19. Examples include inhibitors of RNA-dependent RNA polymerase (remdesivir, favipiravir, ribavirin), viral protein synthesis (ivermectin, lopinavir/ritonavir), and fusion of the viral membrane with host cells (chloroquine, hydroxychloroquine, nitazoxanide, and umifenovir). This article also presents the intellectual groundwork for the ongoing development of vaccines in preclinical and clinical trials, explaining potential candidates (live attenuated-whole virus vaccines, inactivated vaccines, subunit vaccines, DNA-based vaccines, protein-based vaccines, nanoparticle-based vaccines, virus-like particles and mRNA-based vaccines). Designing and developing an effective vaccine (both prophylactic and therapeutic) would be a long-term solution and the most effective way to eliminate the COVID-19 pandemic.

An updated systematic review of Zika virus-linked complications

Objective:To determine the breadth of Zika virus (ZIKV)-associated brain anomalies in neonates and adults.Methods:Systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement using electronic databases ScienceDirect, Pubmed, Medline, Scopus, and Global Health Library. Only those research articles, case studies, case-control studies, case-cohort studies, cross-sectional studies, and organizational survey reports were included in the study that reported any fetal outcomes for pregnant women who had infected with ZIKV during the gestational period and ZIKV-related neurological complications in adults as well.Results:Out of total 72 retrieved articles, 50 met the inclusion criteria. We estimated a significant increase in incidence of neural abnormalities such as Guillain-Barre syndrome and microcephaly in the regions that are experiencing ZIKV outbreaks. Other neurological malformations found in ZIKV patients include hydrancephaly/hydrops fetalis, myasthenia gravis, meningoencephalitis and myelitis.Conclusion:Our systematic analysis provides the broad spectrum of neurological malformations in ZIKV infected patients and these data further support the causal link of ZIKV with neurological disorders.

An updated systematic review of Zika virus-linked complications

Objective: To determine the breadth of Zika virus (ZIKV)-associated brain anomalies in neonates and adults. Methods: Systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement using electronic databases ScienceDirect, Pubmed, Medline, Scopus, and Global Health Library. Only those research articles, case studies, case-control studies, case-cohort studies, cross-sectional studies, and organizational survey reports were included in the study that reported any fetal outcomes for pregnant women who had infected with ZIKV during the gestational period and ZIKV-related neurological complications in adults as well. Results: Out of total 72 retrieved articles, 50 met the inclusion criteria. We estimated a significant increase in incidence of neural abnormalities such as Guillain-Barre syndrome and microcephaly in the regions that are experiencing ZIKV outbreaks. Other neurological malformations found in ZIKV patients include hydrancephaly/hydrops fetalis, myasthenia gravis, meningoencephalitis and myelitis. Conclusion: Our systematic analysis provides the broad spectrum of neurological malformations in ZIKV infected patients and these data further support the causal link of ZIKV with neurological disorders.

study of the interaction between H. pylori mice passage strains and gastric epithelial cells

Helicobacter pylori [H. pylori] infections are very serious health problem that are further worsened by increasing/developing resistance to the current antibiotics. Therefore, new therapeutic agents are needed for H. pylori eradication. Use of a CD46 derived peptide [P3] as bactericidal agent against H. pylori has shown high activity rate in vivo and this study examines the changes in H. pylori features in response to effect of P3 treatment.AGS cells were infected with H. pylori wild type strain 67:21 and its mice passage strains [P3 treated and untreated strains] and further examined using immunoblotting assay, FACS and Urease activity analysis. Comparatively we found increased level of Urease alpha subunit A [UreA] and alkyl hydroperoxide reductase C [AhpC] proteins for P3 treated strain of H. pylori than its wild type or untreated strain after infection of AGS cells. Conclusion These results suggest that there might be a high rate of adherence to host cells for the P3 treated passage strain than untreated or wild type strain. Our findings also indicate that either adhesins are being changed or H. pylori interaction to the host cells is affected after P3 treatment

Advances in research on Zika virus

Zika virus (ZIKV) is rapidly spreading across the America and its devastating outcomes for pregnant women and infants have driven this previously ignored pathogen into the limelight. Clinical manifestations are fever, joint pain or rash and conjunctivitis. Emergence of ZIKV started with a first outbreak in the Pacific area in 2007, a second large outbreak occurred in the Pacific in 2013/2014 and subsequently the virus spread in other Pacific islands. Threat of explosive global pandemic and severe clinical complications linked with the more immediate and recurrent epidemics necessitate the development of an effective vaccine. Several vaccine platforms such as DNA vaccine, recombinant subunit vaccine, ZIKV purified inactivated vaccine, and chimeric vaccines have shown potent efficacy in vitro and in vivo trials. Moreover, number of drugs such as Sofosbuvir, BCX4450, NITD008 and 7-DMA are ready to enter phase I clinical trial because of proven anti-ZIKV activity. Monoclonal based antibodies offer promise as an intervention effective for use in pregnant women. In this review, we describe the advances in research on ZIKV such as research strategies for the development of antiviral drugs & vaccines, molecular evolution, epidemiology emergence, neurological complications and other teratogenic outcomes as well as pathogenesis.

Advances in research on Zika virus

Zika virus (ZIKV) is rapidly spreading across the America and its devastating outcomes for pregnant women and infants have driven this previously ignored pathogen into the limelight. Clinical manifestations are fever, joint pain or rash and conjunctivitis. Emergence of ZIKV started with a first outbreak in the Pacific area in 2007, a second large outbreak occurred in the Pacific in 2013/2014 and subsequently the virus spread in other Pacific islands. Threat of explosive global pandemic and severe clinical complications linked with the more immediate and recurrent epidemics necessitate the development of an effective vaccine. Several vaccine platforms such as DNA vaccine, recombinant subunit vaccine, ZIKV purified inactivated vaccine, and chimeric vaccines have shown potent efficacy in vitro and in vivo trials. Moreover, number of drugs such as Sofosbuvir, BCX4450, NITD008 and 7-DMA are ready to enter phase I clinical trial because of proven anti-ZIKV activity. Monoclonal based antibodies offer promise as an intervention effective for use in pregnant women. In this review, we describe the advances in research on ZIKV such as research strategies for the development of antiviral drugs & vaccines, molecular evolution, epidemiology emergence, neurological complications and other teratogenic outcomes as well as pathogenesis.

Zika: As an emergent epidemic

Zika virus is a new global threat for 2016 that has been swept to almost all Americas and is now posing serious threats to the entire globe. This deadly virus is playing havoc to unborn lives because of its reported association with upsurge of fetal deformation called microcephaly and neuropathic disorders including Guillain-Barré syndrome. Till today, there is no vaccine prospect, antiviral therapy or licensed medical countermeasures to curb the teratogenic outcomes of this destructive viral infection. Diagnosis, treatment, chronicity and pathogenesis are still vague and unsettled. Therefore, this review article addresses all the aspects related to this disease to mitigate the explosive rise in Zika virus infection.

Zika: As an emergent epidemic

Zika virus is a new global threat for 2016 that has been swept to almost all Americas and is now posing serious threats to the entire globe. This deadly virus is playing havoc to unborn lives because of its reported association with upsurge of fetal deformation called microcephaly and neuropathic disorders including Guillain-Barré syndrome. Till today, there is no vaccine prospect, antiviral therapy or licensed medical countermeasures to curb the teratogenic outcomes of this destructive viral infection. Diagnosis, treatment, chronicity and pathogenesis are still vague and unsettled. Therefore, this review article addresses all the aspects related to this disease to mitigate the explosive rise in Zika virus infection.

Liraglutide in diabetes mellitus: more facts and findings

Liraglutide exert favorable effects on most of the diabetes associated cardiovascular [CV] risk factors and this study was designed to further explore the benefits of liraglutide by observing its effect on plasma sialic acid [PSA] in diabetic rats. A total of 30 streptozotocin induced [50mg/Kg; i. p] diabetic rats were randomized into vehicle treated [1 ml/Kg s.c, twice daily] group I, liraglutide treated groups II and III [30 micro g/Kg and 150 micro g/Kg, twice daily respectively] and studied for 6 weeks. Liraglutide treated groups showed significant reductions in fructosamine levels [p

Effects of social barriers on the contraceptive use among males and females in PNS-SHIFA hospital Karachi

Objective: To evaluate the social barrier that influence males and females for using contraception and to evaluate the association of educational status and age with the use of contraceptives

Materials and Methods: This cross sectional study was conducted at PNS SHIFA hospital, Bahria University Medical and Dental College [BUMDC] from 1st July 2015 till 1st September 2015. A predesigned questionnaire was used for the study. 350 participants were included and sampling technique of non-probability convenient sampling was followed. Data was analyzed on SPSS version 23

Results: Out of 96 males, 18 used contraceptives while in females out of 254 only 84 were using it. When assessed the relationship between education and contraceptive use, p-value for males was 0.026 which was highly significant whereas, in females it was non-significant. The top most reasons among non-users were desire to have children, lack of knowledge in males and in females' husband's opposition and non interest. Maximum use of contraception was observed between 34-41 years of age among both males and females

Conclusion: The social barriers that influenced males from using contraception were: wanted to have children, lack of knowledge, religious views whereas, in females they were husband's opposition, lack of interest and fear of side effects. There is need to improve the education status of females. Religious scholars must play their role to increase use of contraception

Laparoscopic Spleenectomy.

Spleen is the largest reticuloendothelial organ in the body consisting of an encapsulated mass of vascular and lymphoid tissue and responsible for defensive actions and hence the name defense organ for it. Like any other organ in the body it is also afflicted by a number of disorders among which are splenic cysts. Herein we report a case of large primary splenic cyst that was treated successfully by laparoscopic Spleenectomy.

Dynamization versus static antegrade intramedullary interlocking nail in femoral shaft fractures

Objective: to compare the primary dynamic interlocking technique with static interlocking method for femoral shaft fractures in terms of bony union

Study design: quasi experimental study

Place and Duration of study: department of Orthopaedic Surgery, Ziauddin University Hospital Karachi, from March 2012 to August 2013

Methodology: all patients with closed femoral shaft fractures were treated by closed reamed intramedullary [IM] interlocking nail. They were divided into two equal groups. Group I [Dynamization group] patients underwent primary dynamization and in Group II [Static group] patients the static nail was used. Both groups were divided into subgroups on the bases of post reduction intrafragmental gap less than or more than 3mm on x-ray.The surgical procedure and postoperative protocols were same for both the groups, with the exception of interlocking mode. The outcome was measured using Thorensen clinical criteria. Bony union, time of union, delayed union, nonunion, implant breakage and leg shortening were recorded

Results: a total of 64 patients were included, 32 in each group. Mean time of union was same in dynamic group and static group with post reduction intrafragmental fracture gap < 3mm. In the dynamic group with post reduction intrafragmental fracture gap=3mm, one case of nonunion was noted. In static group two cases of delayed union and one case of nonunion were noted in sub group with post reduction intrafragmental fracture gap=3mm

Conclusion: dynamization significantly shortened the mean time to union in femoral shaft fracture with intrafragmental gap =3mm, though it did not significantly affect the union rate of the femoral shaft fractures as compared to static close intramedullary interlocking nailing

Cellular and genomic toxicity produced by UV light in Chinese hamster ovary cells

UVB and UVC toxicity was detected in Chinese Hamster Ovary [CHO] cell lines AA8, UV5 and XEM2 [a V79-derived cell line expressing rat P 450 1A1]. Unlike FICZ-HPLC assay that showed induction of CYP1A1 enzyme activity after 20 minutes and 2 hour UVC exposure, the EROD assay showed no difference in cytochrome P450 1A1 [CYP1A1] activity after exposure to different doses of UVB and UVC light. Different cytotoxic and mutagenic effect of photo lesions induced by UVC and UVB light was investigated with the DRAG and HPRT assays, comparing the wild type cell line AA8 and the Nucleotide Excision Repair [NER] deficient cell line UV5. DRAG assay showed a significant difference in UV induced cytotoxicity between UVC and UVB reflecting the larger energy and toxic effect of UVC along with significant difference in UV induced toxicity between AA8 and UV5 cell lines. This was further validated through the HPRT assay, which also showed a significant difference in UVC [5 J/m[2]] induced mutagenic effect between these cell lines. In addition, HPRT assay showed the mutagenic effect of photosensitizer, acetophenone. These results show that UVB and UVC generate serious damage through photo products on DNA, and might induce the metabolic activity of CYP1A1

Pattern of ocular trauma in District Swabi

Background: Ocular trauma is a significant proportion of emergency presentations

Objectives: This study was conducted to determine the pattern of ocular trauma presented in the ophthalmic casualty room of the secondary care hospital in District Swabi

Subject and Methods: This cross-sectional, descriptive study was conducted at the Eye Department of District Head Quarter Hospital, Swabi, over a period of two years; from 1[st] March, 2010 to 28[th] February, 2012. Five hundred and Six patients who presented with ocular trauma either through the outpatient or emergency department were included in the study. The patients demographic data, medical history, detailed examination and final diagnosis were recorded in a questionnaire. Statistical analysis were based on age, gender, presentation, ocular features and diagnosis

Results: Total of five hundred and six patients were included in the study. Male were 77.7% [n=393] and female were 22.3% [n=113]. One hundred and forty five [28.7%] patients were workers while 17.8% [n=90] were housewife. Most of the patients [56.5%, n= 286] reported within few hours of trauma. Home [29.1%] and workplace [26.3%] was common place of injury. Mechanical trauma was observed in 80% [n= 405] of patients. Accidental trauma caused by wood [11.8%], assault due to finger/ fist [26%] and sports related trauma caused by ball [40%] was common. Presenting visual acuity was hand movement in 32% [n=162] patients. Both globe and extra globe injuries [44.5%], extra globe injuries [23.7%], globe injuries [23.3%] and complex injuries [8.5%] were noted. In globe injuries, open globe injuries [OGI] were 42.4%, corneal perforation was most common in 36% patients. Close globe injury was present in 28% patients, punctuate keratitis observed in 29.5% patients. Eyelid was commonly injured [63%] in extra globe injuries. Full thickness laceration was found in 38.9% patients

Conclusion: Traumatic globe, adnexal and open globe injuries are the main ocular emergencies seen. Majority of ocular trauma is preventable. It can be assumed that health education, as well as application of safety measures and regulations, will significantly reduce the incidence of ocular injuries

Bilateral irreversible blindness

To find out the causes of bilateral irreversible blindness in patients of different age groups in District Swabi. It is a prospective observational study of one hundred and eighty nine consecutive blind cases. The study was conducted from July 2010 to June, 2012 at the Ophthalmology Department of District Headquarter Hospital, Swabi. Informed consent was taken from the patient or guardian of the patient. Patients fulfilling inclusion and exclusion criteria were included in the study. A standard proforma was designed and entries were made regarding present, past and family history, thorough ocular examination of every patient was performed on slit-lamp with relevant biomicroscopic aids and posterior segment examination was conducted with direct as well as indirect ophthalmoscope. Biomicroscopy was performed as and when required. lntraocular pressure using schiotz tonometer, corneal diameters, retinoscopy and ocular mobility were noted and relevant investigations were performed when needed. Children and mentally retarded patients were examined using short general anaesthesia. Of 189 patients 61.4% were males and 38.6% were females. Congenital Causes were present in 49.7% and acquired causes in 50.3%. Diseases accounted for 88.9%, trauma in 10.1% and unknown causes in 1.1% cases. Congenital diseases included congenital glaucoma in 35.1%, retinitis pigmentosa in 29.7% and albinism in 19.1% cases. Acquired diseases included primary glaucoma in 33.8%, diabetic retinopathy 23 %, secondary glaucoma in 17.5% and childhood infection in 10.8% cases. Corneal findings included corneal opacity in 31.2%, corneal edema in 4.8% and absent cornea in 7.4%. Optic nerve findings included optic atrophy in 16.4%, glaucomatous optic atrophy in 16.9%, new vessels in 9.5%. Retina findings included retinal dystrophy in 14.3%, maculopathy in 5.3%, chorioretinopathy in 0.5%, vascular retinopathy and hypopigmentation in 9.5% each respectively. Irreversible blindness is more common in children and young adults and mostly males are affected. Glaucoma is the commonest cause followed by retinitis pigmentosa and albinism in this study

Frequency and pattern of ocular emergency in district Swabi

Objectives: To determine the frequency and pattern of ocular conditions presented to the ophthalmic casualty room at a secondary care hospital in District Swabi

Study design: Descriptive Cross- sectional study

Place and duration of study: Eye Department of District Head Quarter Hospital, Swabi over a period of two years from 1[st] March 2010 to 28[th] February 2012

Methodology: Nine hundred and Sixty patients who presented either with acute ocular condition or ocular injury through the outpatient or emergency routes were included in the study. The patients demographic data, detailed history, examination and final diagnosis were recorded in a questionnaire. Statistical analysis was based on age, gender, presentation, ocular features and diagnosis

Results: In our study male were 57.8% [n=555] and female were 42.2% [n=405]. Five hundred and thirty Six[55.8%] patients were in traumatic group while four hundred and twenty four [44.2%] patients were in non-traumatic group. Infective conjunctivitis [62.2%], Stye [12.6%], corneal ulcer [10.10%], retinal vascular disease [1.2%], acute post operative endophthalmitis [1.1%], acute uveitis [2.6%] and acute glaucoma [1.0%] were the leading causes in the non-traumatic group. In traumatic group 94.2% patients were non-infected while 5.8% were infected. In non-infected patients, both globe and extra globe injuries [44.6%], extraglobe injuries [23.8%] and globe injuries[23%] were present. In globe injuries, open globe injuries [OGI] were 39.7%.Post traumatic endophthalmitis was reported in 54.8% of traumatic ocular infection. Mechanical injuries [70.7%] were leading the list of traumatic ocular emergency. Work place [31.5%] was the most common place for ocular trauma

Conclusion: Common non- traumatic ocular emergency were Infective conjunctivitis, infective keratitis, acute glaucoma and acute uveitis. Females mostly middle age housewives had non-traumatic ocular emergencies. Traumatic ocular emergency commonly reported were both globe and extra globe injuries and open globe injuries. Males mostly young workers had traumatic ocular emergency. Mechanical injuries mostly the result of occupational accidents in workers

Radiological evaluation of the stability of crossed-pins versus lateral-pins fixation in displaced supracondylar fractures of humerus

To compare the radiological evaluation of stability of closed reduction of supracondylar fractures of humerus treated by percutaneous two-crossed-pin fixation and 2-lateral pin fixation. Randomized controlled trial. Orthopedic Unit Hayatabad Medical Complex Peshawar, from January 2008 to July 2009. Fifty patients with displaced supracondylar fracture of humerus presented between ages 1-12 year were randomly allocated in two groups of 25 patients each and were subjected to crossed-pin fixation and 2-lateral pin-fixation. Primary outcome measure was determined with the help of Baumann angle. Secondary outcome measure was determined with the help of Metaphyseal-Diaphyseal [MD] angle. Mean age of patients was 7.02 +/- 2.25 year. Mean loss of Baumann angle and Metaphyseal Diaphyseal angles were 5.360 +/- 2.220 and 2.420 +/- 1.250 respectively. The mean Baumann angle loss in the two cross pins fixation group and the 2-lateral pins fixation group were 5.56° +/- 1.80° and 5.16° +/- 2.64° respectively. The mean MD angle loss in the two crossed pins fixation group and the 2-lateral pins fixation group was 2.440 +/- 1.220 and 2.400 +/- 1.230 respectively. When loss of Baumann and Metaphyseal-Diaphyseal angles were compared between two methods of fixation using Student t test, no significant difference in the stability of two methods of pin fixation was observed. Radiological analysis showed that both the techniques were effective in terms of stability

Relationship of alloantibody detection with number of blood transfusions

To study the presence of the alloantibodies and their relationship with the number of transfusions. Two hundred subjects undergoing regular blood transfusions with at least 5 pints of blood within last six months were included in the study. Out of 200 patients, 140 [70%] were transfusion depended thalassaemics, 20 [10%] were haemophilics receiving multiple transfusions, 20 [10%] patients were of aplastic anaemia and 20 [10%] patients were with chronic renal failure undergoing haemodialysis. Antibodies were detected in 9/200 [4.5%] subjects. Ninety four patients received 5-50 transfusions, 2.13% developed alloantibodies. Sixty five patients received >50-100 blood transfusions, 6.15% developed alloantibodies. Forty one patients received >100 blood transfusions, 7.31% developed alloantobodies. Frequency of red cell alloantobodies in our transfusion dependent patient population is 4.5%. The risk of developing alloantobodies increased with increasing number of blood transfusion irrespective of underlying disorder.

Outcome of open prostatectomy

To determine the outcome of open prostatectomy in the general surgery department of rural setup. Descriptive case series. Department of Surgery, Fatima Hospital and Baqai Medical University Karachi, from June 2004 to May 2011. All patients with bladder outlet obstruction due to benign prostatic hyperplasia [BPH], operated by transvesical route were included. The parameters evaluated were improvement in International Prostate Symptom Score [IPSS], peak urinary flow [Qmax], postvoid residual urine [PVRU], blood transfusion rate, operative time, duration of catheterization, hospitalization and postoperative complications. There were 107 patients in the series. Mean age was 67 +/- 6 year [SEM=1]. The IPSS improved from 26.53 +/- 3.920 preoperatively to 9.13 +/- 1.797 postoperatively, PVRU from 136.094 +/- 31.802 to 18.86 +/- 5.694, and Qmax from 9.032 +/- 1.940 to 19.952 +/- 2.555. The postoperative complication rate was 46.7%. It included hemorrhage requiring transfusion [n=13 -15%], urinary tract infection [n=10 - 9.3%], wound infection [n=7 - 6.5%], clot retention [n=5 -4.7%], temporary urinary incontinence [n=3 -2.8%], bladder neck stenosis [n=3 - 2.8%], urethral stricture [n=2 -1.9%], suprapubic urinary fistula [n=2 - 1.9%], and epididymo-orchitis [n=1 - 0.9%]. The mortality rate was 0.9%. The mean operative, catherterization and hospitalization duration were 56.23 +/- 9.77 minutes, 7.12 +/- .81 days, and 8.41 +/- 2.28 days, respectively. Open prostatectomy is still a good option for BPH where endourology facilities are not available

Prevalence of antimicrobial resistance and integrons in Escherichia Coli from Punjab, Pakistan

Antimicrobial resistance was studied in Escherichia coli strains isolated from urine samples of 457 patients suffering from urinary tract infection. High prevalence of class 1 integrons (43.56 percent), sulfamethoxazole resistance genes sul1 (45.54 percent) and sul2 (51.48 percent) along with occurrence of quinolone resistance genes was detected in multi drug resistance isolates.