Outcomes of Ventral Onlay Buccal Mucosal Graft Urethroplasty in Bulbomembranous Urethral Strictures Post-transurethral Resection of the Prostate.

OBJECTIVE: To evaluate the outcomes of ventral onlay buccal mucosal graft urethroplasty (VOBMGU) in bulbomembranous urethral strictures after transurethral resection of the prostate. METHODS: After approval of the institutional ethical committee, we retrospectively examined the database of patients diagnosed with post-TURP urethral stricture (PTS) and treated by VOBMGU from January 2020 to January 2022. The patients were evaluated by retrograde urethrogram and voiding cystourethrogram. Follow-up evaluation included assessment of lower urinary tract symptoms, physical examination, uroflowmetry (Q-max and International Prostate Symptom Score) 3, 6, and 12months of follow-up. RESULTS: A total of 30 patients underwent VOBMGU for bulbomembranous PTS were included. The median age of the patients was 63.5 (11.25). The median stricture length was 3.5 (1.5) cm. During follow-up, the mean Q-max significantly increased to 21.1 ± 5.5 mL/s (P < .0001), 20.1 ± 5.4 mL/s (P < .001), and 19.1 ± 5.3 mL/s (P < .003) at 3, 6, and 12months, respectively. IPSS significantly decreased to 8.93 ± 6.37 at the 12-month follow-up mark (P < .0001). Three patients developed stricture recurrence and two patients developed postoperative urinary incontinence. CONCLUSION: VOBMGU in cases of bulbomembranous urethral PTS offered excellent functional outcomes with low stricture recurrence and minimal risk of incontinence. Further prospective studies are warranted to confirm the results.

Lessons from the field: Supporting infection prevention and control and antimicrobial stewardship in Amman, Jordan.

BACKGROUND: To reduce antimicrobial resistance (AMR), appropriate antimicrobial prescribing is critical. In conjunction with Infection Prevention & Control (IPC) programs, Antimicrobial Stewardship Programs (ASP) have been shown to improve prescribing practices and patient outcomes. Low- and middle-income countries (LMIC) face challenges related to inadequate ASP policies and guidelines at both the national and healthcare facility (HCF) levels. METHODS: To address this challenge, the World Health Organization (WHO) created a policy guidance and practical toolkit for implementation of ASPs in LMIC. We utilized this document to support a situational analysis and two-day ASP-focused workshop. In follow-up, we invited these attendees, additional HCF and hospital directors to attend a workshop focused on the benefits of supporting these programs. RESULTS: Over the course of a total three days, we recruited hospital directors, ASP team members, and IPC officers from fifteen different healthcare facilities in Jordan. We describe the courses and coordination, feedback from participants, and lessons learned for future implementation. CONCLUSIONS: Future efforts will include more time for panel-type discussion. which will assist in further delineating enablers and barriers. Also planned is a total three-day workshop; with the first two days being with ASP/IPC teams, and the final third day being with hospital directors and leadership. The WHO policy guidance and toolkit are useful tools to address overuse of antimicrobial agents. Strong leadership support is needed for successful implementation of ASP and IPC. Discussions on quality/safety, as well as cost analyses, are important to generate interest of stakeholders.

Risk as catalyst for positive change: lessons learnt from public health readiness for cholera in Jordan.

This case study highlights how a looming health crisis was leveraged as drivers for positive change for the health sector, in line with the health security agenda. In Jordan, several authorities are mandated by law to manage health emergencies. Following the declaration of outbreaks of cholera in Iraq, Lebanon and Syria, health authorities in Jordan called for a series of emergency meetings during September 2022 to discuss implications around travel and trade as well as shared waters. WHO was part of the consultations and provided guidance on the application of the International Health Regulations 2005. As the risk for cholera importation persisted, the Ministry of Health assumed its leadership role for the overall health sector response while the Jordanian Center for Disease Control assumed a coordinating function. Roles and responsibilities were enshrined in the National Cholera Preparedness and Response Plan. In consideration of the vulnerability of refugee camps and settlements towards Cholera, the existing Jordan humanitarian coordination platforms such as the Health Sector Working Group were used to share information and to coordinate activities. A whole-of-government risk assessment during December 2022 was complemented by a field visit at Zaatari refugee camp. This helped assess the risk and readiness for a cholera outbreak in Jordan and informed priority activities, such as the establishment of a national risk communication and community engagement working group as well as training on case management.

Implementation of one health approach in Jordan: Joint risk assessment of rabies and avian influenza utilizing the tripartite operational tool.

Background Health challenges at the human-animal-environment interface vary and include zoonotic and food-borne diseases as well as antimicrobial resistance. These are serious threats to animal and public health, and account for the majority of emerging and re-emerging conditions or infectious diseases. Reducing zoonotic disease threats requires an understanding of where and why risks exist. To support countries in building multi-sectoral mechanisms to jointly assess the risks at the human-animal-environment interface, a new operational tool is available to complement the existing tripartite guide to addressing zoonotic diseases in countries. The aim of this study is to conduct joint risk assessment (JRA) of rabies and avian influenza in Jordan utilizing the tripartite Joint Risk Assessment Operational Tool (JRA OT). Methods Representatives of sectors that are involved in zoonotic diseases outbreak investigation, control, surveillance and risk assessment, were trained on JRA OT. The operational tool of tripartite guide to addressing zoonotic diseases in countries that was developed by WHO (World Health Organization), FAO (Food and Agriculture Organization of the United Nations) and WOAH (World Organization for Animal Health) was utilized to conduct risk assessment for rabies and H5N1 avian influenza in Jordan. Results The risk assessment outcome for rabies were as follows: Likelihood is high; impact is moderate with moderate level of uncertainty. The impact of the disease is moderate because the virus transmitted only by animal bite in Jordan. The level of uncertainty is moderate due to existence of some gaps in data available from the ministries regarding the surveillance and collection areas of wild animals with feral dogs. The risk assessment outcome for H5N1 AI indicated a low likelihood estimate with moderate uncertainty level. The impact estimate for H5N1 AI in Jordan is moderate with a low level of uncertainty. Conclusions The tripartite JRA OT provides a helpful and easy to follow guide to bring together expertise and information from all relevant sectors to jointly assess risks from zoonotic diseases and contributes to the understanding and management of shared threats at the human-animal-environment interface.

Mucormycosis co-infection in COVID-19 patients: An update.

Mucormycosis (MCM) is a rare fungal disorder that has recently been increased in parallel with novel COVID-19 infection. MCM with COVID-19 is extremely lethal, particularly in immunocompromised individuals. The collection of available scientific information helps in the management of this co-infection, but still, the main question on COVID-19, whether it is occasional, participatory, concurrent, or coincidental needs to be addressed. Several case reports of these co-infections have been explained as causal associations, but the direct contribution in immunocompromised individuals remains to be explored completely. This review aims to provide an update that serves as a guide for the diagnosis and treatment of MCM patients' co-infection with COVID-19. The initial report has suggested that COVID-19 patients might be susceptible to developing invasive fungal infections by different species, including MCM as a co-infection. In spite of this, co-infection has been explored only in severe cases with common triangles: diabetes, diabetes ketoacidosis, and corticosteroids. Pathogenic mechanisms in the aggressiveness of MCM infection involves the reduction of phagocytic activity, attainable quantities of ferritin attributed with transferrin in diabetic ketoacidosis, and fungal heme oxygenase, which enhances iron absorption for its metabolism. Therefore, severe COVID-19 cases are associated with increased risk factors of invasive fungal co-infections. In addition, COVID-19 infection leads to reduction in cluster of differentiation, especially CD4+ and CD8+ T cell counts, which may be highly implicated in fungal co-infections. Thus, the progress in MCM management is dependent on a different strategy, including reduction or stopping of implicit predisposing factors, early intake of active antifungal drugs at appropriate doses, and complete elimination via surgical debridement of infected tissues.

Jordan's Pandemic Influenza Preparedness (PIP): A Reflection on COVID-19 Response.

The COVID-19 pandemic made it clear to the world that better preparedness for future pandemics is paramount. This study aims to explore how the 2018 Jordan's Pandemic Influenza Preparedness (PIP) assessment plan (conducted utilizing a standardized tool of the CDC National Inventory of Core Capabilities for Pandemic Influenza Preparedness and Response) reflected on the initial COVID-19 response. A qualitative, single intrinsic case study design, utilizing interpretivist approach, was utilized to interview subject-matter experts and explore the potential reflection of PIP assessment on COVID-19 response. Utilizing a mini-Delphi approach, the interviews aimed at generating an in-depth understanding of how the Jordan's PIP risk assessment reflects on the country's response to COVID-19. The following 12 core capabilities, along with their reflections on COVID-19, were assessed: country planning, research and use of findings, communications, epidemiologic capability, laboratory capability, routine influenza surveillance, national respiratory disease surveillance, outbreak response, resources for containment, community-based interventions to prevent the spread of influenza, infection control (IC), and health sector pandemic response. Jordan's experience and preparedness for influenza may have served as a crucial guide to establishing success in COVID-19 control and mitigation. Surveillance, outbreak, and research activities were very well established in Jordan's PIP, whereas surge capacity in human capital and health facility were identified as two high-risk areas. However, the limitation in these two areas was met during the COVID-19 response. Still, human capital suffered fatigue, and there was an evident lack of laboratory testing plans when COVID-19 cases increased. Jordan's experience with PIP may have served as a guide for establishing successful COVID-19 control and mitigation. The established PIP principles, systems, and capacities seem to have reflected well on fighting against COVID-19 in terms of more efficient utilization of available surveillance, laboratory, outbreak management, and risk communications. This reflection facilitated a better mitigation and control of COVID-19.

Could allicin alleviate trastuzumab-induced cardiotoxicity in a rat model through antioxidant, anti-inflammatory, and antihyperlipidemic properties?

AIMS: Although trastuzumab (TZB)-induced cardiotoxicity is well documented and allicin (one of the main active garlic ingredients) has ameliorating effects against numerous causes of toxicities; however, the influence of allicin on TZB-induced cardiotoxicity has not been investigated yet. Therefore, the current work explored the potential cardioprotective structural, biochemical, and molecular mechanisms of allicin against TZB-induced cardiotoxicity in a rat's model. METHODS: Forty rats were divided into four equal groups and treated for five weeks. The control group (G1) received PBS, the allicin group (G2) received allicin (9 mg/kg/day), the TZB group (G3) received TZB (6 mg/kg/week), and the allicin+TZB group (G4) received 9 mg of allicin/kg/day +6 mg of TZB/kg/week. Heart specimens and blood samples were processed for histopathological, immunohistochemical, biochemical, and molecular investigations to determine the extent of cardiac injury in all groups. KEY FINDINGS: The myocardium of G3 revealed significant increases in the numbers of inflammatory and apoptotic cells and the area percentage of collagen fibers and TNF-α immunoexpression compared with G1 and G2. Besides, qRT-PCR analysis exhibited significant reductions of SOD3, GPX1, and CAT expressions with significant increases in TNFα, IL-1ß, IL-6, cTnI, cTnT, and LDH expressions. Additionally, flow cytometry analysis demonstrated a significant elevation in the apoptotic and ROS levels. In contrast, allicin+TZB cotherapy in G4 ameliorated all previous changes compared with G3. SIGNIFICANCE: The current study proves that allicin could be used as a novel supplementary cardioprotective therapy to avoid TZB-induced cardiotoxicity via its anti-inflammatory, antifibrotic, antioxidant, antihyperlipidemic, and antiapoptotic properties.

Cytoprotective Antioxidant, Anti-Inflammatory, and Antifibrotic Impact of Celery Seed Oil and Manuka Honey Against Cyclophosphamide-Induced Cystitis in Rabbits.

Patients treated with cyclophosphamide (CP) usually suffer from severe hemorrhagic cystitis (HC). Our previous study exhibited that mesna + celery cotherapy partially ameliorated HC. Therefore, there is a substantial need to seek alternative regimens to get complete protection against CP-induced HC. The current study investigated the effects of mesna + celery seed oil (MCSO) or mesna + manuka honey (MMH) cotherapy against CP-induced HC in adult male rabbits. The forty rabbits were divided into four equal groups and treated for three weeks. The control group (G1) received distilled water and the second group (G2) received CP (50 mg/kg/week). The third group (G3) received CP + MCSO (CPMCSO regimen), and the fourth group (G4) received CP + MMH (CPMMH regimen). The urinary bladder (UB) specimens were processed to evaluate UB changes through histopathological, immunohistochemical, ultrastructural, and biochemical investigations. In G2, CP provoked HC features (urothelial necrosis, ulceration, and sloughing), UB fibrosis, and TNF-α immunoexpression. Besides, CP reduced the activity of antioxidant enzymes (GPx1, SOD3, and CAT) and elevated the serum levels of NF-κB, TNF-α, IL-1B, and IL-6 cytokines in G2 rabbits. In contrast, the CPMMH regimen caused significant increments of UB protection against HC in G4 rabbits compared to the partial protection by the CPMCSO regimen in G3. Therefore, our study indicated for the first time that the novel CPMMH regimen resulted in complete UB protection against CP-induced HC via combined antioxidant, anti-inflammatory, and antifibrotic properties.

Decreased level of plasma nesfatin-1 in rats exposed to cell phone radiation is correlated with thyroid dysfunction, oxidative stress, and apoptosis.

CONTEXT: Exposure to Electomagnetic radiation fields of cell phones causes thyroid dysfunction and a previous study revealed that nesfatin-1 may affect functions of the thyroid gland. OBJECTIVE: To study the role of nesfatin-1 on functions of rat's thyroid gland exposed to EMRF. MATERIALS AND METHODS: Thirty adult male rats were divided equally into 3 groups as group I, group II and group III. The experiment extended for 30 days then the plasma nesfatin-1 level, thyroid functions, and thyroid tissue oxidative stress were assessed. Also; histological and immunohistochemical study studies were done to evaluate structural and apoptotic changes of the thyroid gland. RESULTS: There was a significant decrease in plasma nesfatin-1 level and thyroid functions with an increase in oxidative stress and apoptosis. Interestingly, there was a correlation between nesfatin-1 level and markers of thyroid function, oxidative stress and apoptosis. CONCLUSION: Nesfatin-1 plays a role in thyroid dysfunctions of rats exposed to mobile phone radiation.

Curcumin and ustekinumab cotherapy alleviates induced psoriasis in rats through their antioxidant, anti-inflammatory, and antiproliferative effects.

INTRODUCTION: Psoriasis is a chronic multifactorial inflammatory disease that affects 3% of people worldwide. Ustekinumab is a selective anti-IL-12/23 biologic that alleviates psoriasis, and curcumin is a natural, effective dietary turmeric extract applied to treat numerous diseases through its antioxidant and anti-inflammatory effects. OBJECTIVE: The current study evaluated the therapeutic effects of curcumin and ustekinumab cotherapy (CUC) on imiquimod (IQ)-induced psoriasis in a rat model. MATERIALS AND METHODS: Twenty rats were divided into four groups, G1 (control group), G2 (IQ-treated group), G3 (IQ + ustekinumab), and G4 (IQ + CUC). Clinical, histopathological (HP), immunohistochemical (IHC), antioxidant, and biochemical investigations evaluated the efficacy of these drugs for treating IQ induced-psoriasis. RESULTS: Rats of G2 exhibited clinical signs of psoriatic skin lesions (erythema, scaling, and skin thickening) with epidermal changes (acanthosis and parakeratosis). Additionally, the biochemical analysis revealed significant (p < 0.05) reductions in the levels of antioxidant biomarkers (SOD, GPx, and CAT) with significant (p < 0.05) elevations in psoriasis-related cytokines (TNF-α, IL-17A, IL-12P40, and IL-23). In contrast, CUC alleviated the psoriatic changes in G4 better than ustekinumab monotherapy in G3. CONCLUSIONS: Ustekinumab inhibits the inflammatory cytokines IL-12P40 and IL-23, while curcumin has antioxidant effects (increasing SOD, GPx, and CAT levels) with anti-inflammatory effects (decreasing the proinflammatory cytokine TNF-α and IL-17). Therefore, CUC could be an excellent cost-effective regimen that can improve the treatment of psoriasis by the synergistic effects of CUC.HighlightsIQ-induces psoriasis by elevating TNF-α, IL-17A, IL-12, and IL-23 and decreasing GPx, SOD, and CATUstekinumab exhibits anti-inflammatory effects by inhibiting IL-12 and IL-23Curcumin inhibits TNF-α and IL-17A, and increases GPx, SOD, and CAT levelsCUC mitigates psoriasis by synergistic antioxidant and anti-inflammatory effectsCUC inhibits TNF-α, IL-17A, IL-12, and IL-23 and increases GPx, SOD, and CAT levels.

Garlic Extract Alleviates Trastuzumab-Induced Hepatotoxicity in Rats Through Its Antioxidant, Anti-Inflammatory, and Antihyperlipidemic Effects.

BACKGROUND: Trastuzumab is a new biological drug that has been used to treat breast and gastric cancer; however, its cardiotoxicity and hepatotoxicity limit its use. Garlic has antioxidant, anti-inflammatory, antihyperlipidemic, and anticancer effects. The present study aimed to evaluate the effects of garlic on trastuzumab-induced hepatotoxicity in a rat model. METHODS: Twenty rats were divided into four equal groups as vehicle control (G1), garlic (G2), trastuzumab (G3), and trastuzumab+garlic (G4). All rats were sacrificed after eight weeks of treatment, followed by blood collection and excision of liver tissues for further analyses. The liver specimens were processed for histopathological (HP), immunohistochemical (expression of TNF-α and PCNA), immunofluorescent expression of Chk2 and p53, biochemical, and flow cytometry investigations to evaluate the extent of hepatocyte injury. The biochemical analysis was conducted for the activity of tissue antioxidants (GPX1, CAT, and SOD2), serum lipid profile, and liver enzymes, whereas ROS was performed by flow cytometry. RESULTS: The results revealed remarkable structural changes in hepatocytes of G3 with significant increases in the numbers of inflammatory cells and positive PCNA cells, area % of collagen fibers, and immuno-expression of TNF-α, as well as a significant reduction in the nuclear expression of Chk2. In addition, significant reductions were noticed in the antioxidant enzymes (SOD2, CAT, and GPX1) activity of G3. In contrast, the levels of lipid profile tests (triglycerides, total cholesterol, LDLC, and HDLC), liver enzymes (ALT, AST, and ALP), and ROS revealed significant increases in rats of G3. Likewise, garlic administration in G4 restored all mentioned changes to their average levels deviated by trastuzumab. CONCLUSION: Based on the current results, garlic demonstrates hepatoprotective effects against trastuzumab-induced toxicity in rats. The study suggested for the first time that the coadministration of garlic with trastuzumab for treating breast or gastric cancer can augment their efficacy with minimal toxicity.

Could Mesna and Celery Seed Cotherapy Modulate Oxidative Stress and Inflammation of the Urinary Bladder Induced by Ifosfamide in Rabbits?

BACKGROUND: Ifosfamide (IFS) has potential complications such as nephropathy and hemorrhagic cystitis (HC). Although mesna can prevent IFS-induced cystitis by direct binding and neutralization of acrolein, HC symptoms have still been observed clinically in most of these cases. Celery is a powerful healing vegetable that has antioxidant, anti-inflammatory, and anticancer effects. The current study evaluated the synergistic effects of mesna and celery seed on IFS-induced HC in rabbits. METHODS: Twenty male rabbits (four groups) were administered distilled water, IFS, mesna, and mesna+celery seed cotherapy (MCC) for three weeks. The serum and urinary bladder of experimental rabbits underwent biochemical (TNF-α, MDA, iNOS, SOD, GPx, and CAT), histopathological and ultrastructural investigations to evaluate the structural changes of the urinary bladder (UB). RESULTS: IFS injection resulted in severe cystitis with a remarkable increase in the scale of hematuria, elevations of TNF-α, MDA, and iNOS activity, and reduced activity of SOD, GPx, and CAT antioxidants. Additionally, the structure of UB exhibited evident mucosal edema and ulceration. In contrast, the MCC regimen group revealed partial synergistic improvement of all mentioned parameters. CONCLUSION: IFS induced cystitis by releasing acrolein, which exerted a significant role in the pathogenesis of HC. In contrast, the MCC intake partially ameliorated the UB damage through its antioxidant and anti-inflammatory effects.

Prevalence and associated factors of respiratory allergies in the Kingdom of Saudi Arabia: A cross-sectional investigation, September-December 2020.

BACKGROUND: Prevalence of different respiratory allergies is increasing in the Kingdom of Saudi Arabia (KSA). Environmental risk factors of respiratory allergy vary regionally, hence the prevalence. This necessitates the needs for regional studies. This article reports prevalence and symptoms of respiratory allergies in the Qassim region, and the factors associated with the prevalence. METHODS: Eight hundred and fifty individuals aged ≥18 years and were living in the Qassim region filled up our structured online questionnaire between September and December 2020. We estimated the prevalence of different respiratory allergies with 95% confidence intervals. Multi-variable logistic regression analyses were performed to investigate the risk factors of respiratory allergies. FINDINGS: The prevalence of any respiratory allergy in the Qassim region was 28.8%. Most families (58.1%) had at least one member with respiratory allergy. The prevalence of allergic rhinitis and bronchial asthma were 13.5% and 11.2% 4.1% respectively. The reported symptoms included runny nose (13.6%), red, watery, and itchy eyes (10.4%), difficulty sleeping at night (10.2%), difficulty breathing in cold weather (9.2%), noisy breathing (8.5%), sneezing (8%), repeated coughing (7.5%) and shortness of breath (6.4%). Individuals with a family history were more likely to report any respiratory allergy (OR: 7.8), bronchial asthma (OR: 4.2) and allergic rhinitis (OR: 8.1) compared to the individuals without such family history. Odds of respiratory allergies was higher among males (OR: 1.5). Saudi nationals were less likely to report allergic rhinitis than the non-Saudis (OR: 0.4). Among those who reported a respiratory allergy, most (73.5%) received treatment and majority (61.7%) demonstrated compliance to the treatment, 8.8% needed hospitalization, and 23.1% needed emergency nebulization. CONCLUSIONS: Prevalence reported in our study is different than that reported in other regions. Variability in the environmental exposures might explain this. We recommend a meta-analysis to estimate the national prevalence of respiratory allergies.

Thyme oil alleviates Ova-induced bronchial asthma through modulating Th2 cytokines, IgE, TSLP and ROS.

Bronchial asthma (BA) is a heterogeneous allergic respiratory disease with diverse inflammatory symptoms, pathology, and responses to treatment. Thyme is a natural product which is consisted of multiple phenolic compounds of therapeutic significance for treatment of cough and bronchitis. This study evaluated the efficacy of thyme oil against ovalbumin (OVA)-induced BA in an experimental rabbit model. Forty male rabbits were divided into four equal groups [control group (G1), OVA (G2), thyme oil (G3), and OVA plus thyme oil (G4)]. Animals were treated for 30 days, and clinical, histopathological (HP), histochemical (HC), immunohistochemical (IHC), morphometric, biochemical and flow cytometry methods were performed, followed by statistical analysis. All used methods revealed normal structure of the lung tissues in rabbits of G1 and G3. In contrast, the clinical examination of G2 rabbits revealed an obvious increase in the respiratory rate, sneezing and wheezing, whereas the HP, HC and IHC techniques exhibited substantial inflammatory changes in the peribronchio-vascular lung tissues with thinning, degeneration, apoptosis (using the TUNEL assay), necrosis, and shedding of the airway epithelium. Furthermore, the morphometric results confirmed significant increases in the numbers of inflammatory cells, goblet cells, eosinophils and apoptotic cells from (12, 0, 2, 2 cells) to (34,10, 16, 18 cells) respectively, as well as the area percentage of collagen fiber deposition and immunoexpression of eotaxin-1/10 high power fields. Additionally, the biochemical results revealed significant increases in the serum levels of TSLP, IL-4, IL-5, IL-9, IL-13, IgE and eotaxin-1 cytokines from (140, 40, 15, 38, 120, 100, 48) pg./ml to (360, 270, 130, 85, 365, 398, 110) pg./ml respectively, while analysis of ROS by flow cytometry revealed remarkable oxidative stress effects in G2 rabbits. On the other hand, treatment of rabbits with thyme oil in G4 substantially alleviated all OVA-induced alterations. Overall, our findings indicate for the first time that thyme oil can ameliorate OVA-induced BA via its immunomodulatory, anti-inflammatory, antiapoptotic, and antioxidant effects on the lung tissues of rabbits.

L-carnosine mitigates interleukin-1α-induced dry eye disease in rabbits via its antioxidant, anti-inflammatory, antiapoptotic, and antifibrotic effects.

OBJECTIVE: To elucidate the implications of L-carnosine on interleukin-1α (IL-1α)-induced inflammation of lacrimal glands (LGs). MATERIALS AND METHODS: Forty rabbits were divided equally into four groups: control group (G1), IL-1α (G2), L-carnosine (G3), and L-carnosine plus IL-1α (G4). Several clinical, histopathological, immunohistochemical, morphometric, and biochemical investigations were performed, followed by statistical analysis to diagnose the presence of dry eye disease (DED). RESULTS: The LGs of G2 rabbits showed degeneration of the acinar cells, increased deposition of collagen fibers, and marked immunoexpression of FasL; elevated levels of interferon-γ, tumor necrosis factor-α, transforming growth factor-ß1, and malondialdehyde; and decreased levels of glutathione peroxidase, superoxide dismutase, catalase, and reactive oxygen species compared with those of G1 rabbits. In contrast, administration of L-carnosine to G4 rabbits revealed marked improvement of all previously harmful changes in G2 rabbits, indicating the cytoprotective effects of L-carnosine against IL-1α-induced inflammation of LGs. CONCLUSIONS: IL-1α induced inflammation of LGs and eye dryness via oxidative stress, proinflammatory, apoptotic, and profibrotic effects, whereas L-carnosine mitigated DED through antioxidant, anti-inflammatory, antiapoptotic, and antifibrotic effects on LGs. Therefore, this work demonstrates for the first time that L-carnosine may be used as adjuvant therapy for the preservation of visual integrity in patients with DED.HighlightsIL-1α induced dry eye disease through its oxidative stress, proinflammatory, apoptotic and profibrotic effects on the lacrimal glands of rabbit.L-carnosine has antioxidant, anti-inflammatory, antiapoptotic and antifibrotic effects.L-carnosine mitigated IL-1α induced dry eye disease via elevating the levels of FasL, IFN-γ, TNF-α, TGFß1 and MDA as well as reducing the levels of antioxidants (GPx, SOD, and catalase) and ROS in the lacrimal glands of rabbit.L-carnosine could be used as a novel adjuvant therapy for the treatment of dry eye disease.

Irisin Has a Protective Role against Osteoporosis in Ovariectomized Rats.

The reduction in estrogen levels results in a decrease in bone density at menopause. Irisin is a myokine that modulates the benefits of exercise, which may include bone health. This study was planned to examine irisin's impact in preventing osteoporosis after ovariectomy. 4 groups of female albino rats (10 rats/group): control, sham-operated, ovariectomized (OVX-control), and OVX-irisin-treated. Serum levels of bone markers [osteocalcin (OC), bone alkaline phosphatase (BALP), tartrate-resistant acid phosphatase (TRAP), calcium (Ca++), phosphorus (P)], glucose, and insulin were being measured. Body mass index, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), dry and ash femur weight, and bone contents of Ca++ and P were investigated. The femur was examined histopathologically. The OVX-control group showed an increase in serum levels of OC, BALP, TRAP, calcium, phosphorus, BMI, glucose, insulin, and HOMA-IR (P < 0.05) and a reduction in dry and ash weight of the femur, the concentration of calcium and phosphorus content in bone ash (P < 0.05). The OVX-irisin-treated group exhibited a decrease in serum levels of OC, BALP and TRAP, calcium, phosphorus, BMI, glucose, insulin, HOMA-IR (P < 0.05), and a rise in dry and ash weight of the femur, the concentration of calcium and phosphorus in bone ash (P < 0.05). Histological examination of the distal femur diaphysis of the OVX-irisin-treated group exhibited proper bone architecture and density compared with that of the OVX-control group. It is concluded that irisin treatment in the OVX rats safeguarded the regular bone architecture and normal levels of serum bone biomarkers. Irisin may be a possible novel target in the prohibition of postmenopausal osteoporosis.

Diallyl Sulfide-Mediated Modulation of the Fatty Acid Synthase (FASN) Leads to Cancer Cell Death in BaP-Induced Lung Carcinogenesis in Swiss Mice.

PURPOSE: Diallyl sulfide (DAS), one of the organo-sulfur secondary metabolites in garlic, has been shown to inhibit the proliferation of cancer cells. The present study aimed to evaluate the mechanism of DAS in the prevention of benzo[a]pyrene (BaP)-induced lung cancer in a murine model. MATERIALS AND METHODS: The mice were exposed to 50 mg/kg of BaP twice a week for 4 weeks in order to induce lung carcinoma. Pretreatment of mice with DAS (100 mg/kg) was started 2 weeks before BaP exposure and further continued for 21 weeks. The effect of DAS and BaP was evaluated by studying various parameters in the serum and tissues of the treated or untreated BaP-exposed mice. RESULTS: The histopathological findings demonstrated that DAS prevented the progression of malignant lung cancer and metastasis in the liver. A significant drop was observed in BaP-induced tumor marker enzymes (ADA, AHH, γ-GT, LDH) in the serum of the mice treated with DAS. Moreover, DAS treatment resulted in the recovery of antioxidant enzymes, SOD and CAT, in BaP-exposed mice. The induction of apoptosis and the destruction of cellular ROS were detected in cancer cells from the mice pre-treated with DAS. The immunohistochemical analysis revealed the up-regulation of fatty acid synthase (FASN) in the lungs and liver tissues of BaP-exposed mice and the treatment with DAS inhibited FASN expression. CONCLUSION: The findings of the present study indicated that DAS-induced apoptosis is strongly associated with the downregulation of FASN in tumor tissues. To the best of our knowledge, this is the first study that describes the role of FASN in BaP-induced lung carcinogenesis.

Corrigendum to "GC Method Validation for the Analysis of Menthol in Suppository Pharmaceutical Dosage Form".

[This corrects the article DOI: 10.1155/2017/1728414.].

Formulation and In Vitro, In Vivo Correlation Between Two Candesartan Cilexetil Tablets.

In this study, the in vitro and in vivo interchangeability between generic candesartan 16 mg and the branded formulation was assessed. The in vitro release of these products was conducted in 3 pH media (1.2, 5.0, and 6.8), and similarity factors (f2 ) were calculated. This bioequivalence study was a randomized, 2-period crossover study that included 42 healthy adult male subjects under fasting conditions with a 9-day washout. The pharmacokinetic (PK) parameters AUC0-last , AUC0-∞ , and Cmax , tmax , and the elimination half-life time were assessed based on the plasma concentrations of candesartan, using a newly developed and validated liquid chromatography-tandem mass spectrometry bioanalytical method with acceptable degrees of linearity, sensitivity, precision, and accuracy. The geometric mean (ng·h/mL) of the AUC0-∞ for the test and brand was 1595.49 and 1620.54, respectively, and the Cmax (ng/mL) was 160.91 and 160.88, respectively. The 90%CIs of geometric mean ratios (test-to-reference ratios) were 98.26%, 98.45%, and 99.86% for AUC0-last , AUC0-∞ , and Cmax respectively. These PK parameters lie within the US Food and Drug Administration- and European Medicines Agency-specified bioequivalence limit (80%-125%). Both products were well tolerated by all the subjects. The tested drug product was bioequivalent to the reference drug and had the same safety profile.

GC Method Validation for the Analysis of Menthol in Suppository Pharmaceutical Dosage Form.

Menthol is widely used as a fragrance and flavor in the food and cosmetic industries. It is also used in the medical and pharmaceutical fields for its various biological effects. Gas chromatography (GC) is considered to be a sensitive method for the analysis of menthol. GC chromatographic separation was developed using capillary column (VF-624) and a flame ionization detector (FID). The method was validated as per ICH guidelines for various parameters such as precision, linearity, accuracy, solution stability, robustness, limit of detection, and quantification. The tested validation parameters were found to be within acceptable limits. The method was successfully applied for the quantification of menthol in suppositories formulations. Quality control departments and official pharmacopeias can use our developed method in the analysis of menthol in pharmaceutical dosage formulation and raw material.