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Abstract: COVID-19 is caused by the SARS-CoV-2 virus, which has afflicted more than 245.37 million individuals worldwide and resulted in more than 4.9 million deaths as of today, with a mortality rate of 2.1%. Diabetes mellitus (DM) and its secondary complications are the major serious global health concerns today due to its growth rate, and it is the fastest-growing non-communicable disease. According to International Diabetes Federation (IDF) data, one out of 11 adults is diabetic, and the projection says that the figure will reach 642 million by 2040 globally. The occurrence of DM and its secondary complications is also associated with the severity of COVID-19 and high mortality. People with DM have a weakened immune system owing to innate immunity defects affecting phagocytosis, neutrophil chemotaxis, and cellmediated immunity; however, the high prevalence of diabetes in serious cases of COVID-19 may reflect the higher prevalence of type 2 DM (T2DM) in older people. Moreover, DM is linked to cardiovascular illness in older people, which could underlie the correlation between COVID-19 and fatal outcomes. SARS-CoV-2 infects via the angiotensin-converting enzyme 2 (ACE2), which is found in pancreatic islets, and infection with SARS-CoV-1 has been linked to hyperglycemia in individuals who do not have DM. And hence diabetic patients need to take more precautions and maintain their blood glucose levels. Many pieces of research say that COVID-19 and DM, especially its secondary complications are interlinked. But it also needs more elaborative evidence on whether the anti-diabetic drugs can manage only blood glucose or SARS-CoV-2.

To illustrate the differential outcome of atorvastatin versus rosuvastatin on matrix metalloproteinases (MMP-9) in patients with acute ischaemic stroke (AIS).The case-control study was done in the Department of Clinical Pharmacology and Therapeutic, Mustansiriyah University, Baghdad, Iraq, from March to June, 2020 and involved 66 AIS patients and 22 healthy controls. They sub-grouped into Group A: AIS patient on statins therapy (n=44), with 22 on atorvastatin and 22 on rosuvastatin. Group B: AIS patients not on statins therapy (n=22). Anthropometric, lipid, and pressure profiles were evaluated. As well, MMP-9 level was estimated in different treated groups. SPSS version 20.00 was used for data analysis.MMP-9 level was greater in patients with AIS (19.69±7.49 ng/dL) mainly those not on statin therapy (28.24±12.14 ng/dL) compared to the controls (10.54±1.92 ng/dL), (P=0.003). Regarding the differential effect of statins therapy on MMP-9 serum level in patients with AIS, it was (20.63±5.67 ng/dL) in patients on atorvastatin therapy and (19.69±5.41 ng/dL) in patients on rosuvastatin therapy, (P=0.57). MMP-9 serum level was highly correlated with stroke risk score (SRS) in patients with AIS not on statins therapy (P0.001, r=0.89) as compared with SRS in patients with AIS on statins therapy (P=0.03, r=0.42).MMP-9 is regarded as a surrogate biomarker of AIS in patients with underlying poor cardio-metabolic profile. Both atorvastatin and rosuvastatin are operative in attenuation of AIS measured by lowering of MMP-9 serum levels.

Histamine is a biogenic amine distributed extensively in the human cells. Histamine is linked with different inflammatory and allergic disorders through promoting of chemoatractant activity and endothelial changes. Antihistamine drugs are effective in the treatment and prevention of infection of influenza H7N9 through inhibition of viral entry to the host cells. A multiplicity of search strategies including experimental, preclinical and clinical studies were taken on and assumed to review the potential role of H1, H2 or their combination in the management of Coronavirus disease 2019 (Covid-19). Histamine release is associated with early and late pathology of Covid-19 and clinical presentation. Despite the potential effect of famotidine in attenuating the pathogenesis of Covid-19, famotidine has no direct effect on the replication of SARS-CoV-2. However, azelastine (H1receptor blocker) used for allergic rhinitis as nasal spray has potential anti-SARS-CoV-2 activity comparable to that of remdesivir, lopinavir and chloroquine. Azelastine is more effective than other agents that are used in the management of Covid-19 due to significant inhibition of endosomal acidification at respiratory epithelial cells. However, famotidine and cetirizine combination improve clinical outcome and reduce intubation and duration of hospitalization in Covid-19 patients. Taken together, hospitalised Covid-19 patients treated with famotidine only showed more complications as compared with those treated with combination of famotidine and cetirizine.Both H1 and H2 blockade are effective in the management of Covid-19 patients through antiviral and anti-inflammatory properties, which together reduce the risk of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).

Covid-19 is associated with different neurological manifestations. About one third of Covid-19 patients have some neurological disorders as paresthesia, headache, cold extremities and disturbances of consciousness, which are more evident in severely affected patients. These neurological manifestations may coexist or precede the onset of respiratory manifestations by about 2-3 weeks. Acute ischaemic stroke (AIS) and associated brain damage may develop due to acute respiratory distress syndrome (ARDS) induced-hypoxia. Prolonged hypoxia in late-stage Covid-19 leads to vasodilatation, intracranial hypertension, brain oedema, and AIS. In view of substantial evidence, this perspective explores the potentially direct or indirect effect of SARS-CoV-2 on the Central Nervous System of patients with COVID-19 pneumonia. The AIS is the end of most Covid-19-induced neurological complications. Covid-19 can lead to various neurological manifestations due to involvement of CNS directly through olfactory neurons or indirectly through induction of cytokine storm.

To demonstrate the differential effect of atorvastatin and rosuvastatin on the Intercellular adhesive molecule 1(ICAM-1) in acute ischaemic stroke (AIS) patients.The case-control study was done in the Department of Clinical Pharmacology and Therapeutic, Mustansiriyah University, Baghdad, from May to July, 2020 and involved sixty-six patients with AIS compared with twenty-two healthy controls. They were divided into four groups; Group I: Patients with AIS on atorvastatin therapy (n=22). Group II: Patients with AIS on rosuvastatin therapy (n=22), Group III: Patients with AIS not on statin therapy (n=22), Group IV: Healthy controls (n=22). Anthropometric, lipid, and pressure profiles were evaluated. As well, ICAM-1 serum level was estimated in different treatment groups. SPSS version 20.00 was used for data analysis.ICAM-1 levels were increased in patients with AIS compared to the controls. ICAM-1 serum levels were higher in patients with AIS not on statins therapy compared to the controls (P=0.0001), and it was lower in patients with AIS on statins therapy (77.41±16.46) as compared with patients with AIS not on statin therapy (118.71±10.38), (P=0.001). Besides, there was differential effect of statin therapy on the ICAM-1 serum level, which was higher in patients with AIS on rosuvastatin (72.93±9.03) as compared with patients with AIS on atorvastatin (70.61±10.94), (P=0.44). Stroke risk score (SRS) was lower in patients with AIS on atorvastatin therapy (7.60±2.05) as compared with patients with AIS on rosuvastatin therapy (9.11±2.72), (P=0.04).ICAM-1 is regarded as a surrogate biomarker of AIS in patients with underlying poor cardio-metabolic profile. Both atorvastatin and rosuvastatin are effective in attenuation of AIS measured by lowering of ICAM-1 serum levels.

To elucidate the anti- Methicillin resistance Staphylococcus aureus (MRSA) effect of pomegranate alone and in combination with moxifloxacin fluoroquinolone.A total of five clinical isolates of MRSA (ATCC 43300) were used in the study. Disc diffusion method was used to determine the anti-MRSA effect of pomegranate and/or moxifloxacin by using Mueller-Hinton agar. Minimal inhibitory concentration (MIC), fractional inhibitory concentration (FIC) of moxifloxacin and pomegranate were calculated, the dynamic picture of the bactericidal effect of pomegranate and/or moxifloxacin was determined. SPSS version 20.00 was used for data analysis.Zone of inhibition (ZOI) of moxifloxacin was 19.67±4.84mm which was not significant compared with pomegranate ZOI 14.59±2.73mm, (P=0.07). The combination of moxifloxacin and pomegranate led to more significant ZOI (26.83±4.91mm) compared with moxifloxacin (P=0.04) and pomegranate alone (P=0.0012). MIC of pomegranate was high (31.62±6.95mg/mL) compared with low MIC of moxifloxacin (2.70±0.63 mg/mL), (P0.0001), while MIC of the combination was low (1.22±0.85mg/mL) compared MIC of moxifloxacin, (P=0.012). FIC of pomegranate was 0.038 and FIC of moxifloxacin was 0.45, therefore sFIC index was 0.488, equal to the synergistic effect. The kill rates of combination were higher than those of pomegranate or moxifloxacin, against MRSA ATCC 43300.Ellagic acid-rich pomegranate extract alone has significant antibacterial activity and synergizes the bactericidal effect of moxifloxacin against MRSA.

To investigate melatonin serum level and inflammatory biomarkers in acute toxoplasmosis in pregnant women with recurrent abortions.The case-control study was conducted at the Department of Parasitology, together with the Department of Obstetrics, Al-Yarmouk teaching hospital, Baghdad Iraq, from September 2018 until February 2019. Included were 60 pregnant women in first trimester with acute toxoplasmosis (n=28) or without toxoplasmosis (n=32) and with the history of recurrent abortions with a control group of healthy pregnant women (n=25). Melatonin and interleukins (IL-10, 1L-12) serum levels were evaluated in all groups. The data analysis was done by using SPSS 20.The mean serum melatonin level was lower in the pregnant women with acute toxoplasmosis (69.57±17.37 pg/ml) as compared to the pregnant women without acute toxoplasmosis (77.25±24.35 pg/ml), but the difference was not significant (p=0.43). Healthy pregnant women had a higher serum melatonin level (117.48±34.88 pg/ml) compared with the pregnant women with/without acute toxoplasmosis and a history of recurrent abortions. IL-10 serum level was higher in the healthy controls (12.73±2.58 pg/ml) as compared with the pregnant women with acute toxoplasmosis (5.50±1.92pg/ml) or without acute toxoplasmosis (8.50±2.53 pg/ml), (p0.0001). Serum melatonin level was positively correlated with serum IL-10 level (P0.001, r=0.94), and negatively correlated with serum IL-12 level in pregnant women with recurrent abortions with or without acute toxoplasmosis.Acute toxoplasmosis during pregnancy increases the risk of abortion through reduction of maternal serum melatonin level and dysregulation of pro-inflammatory/inflammatory cytokines axis.

To illustrate the role of neuropeptide Y (NPY), agouti-related-peptide (AgRp) and their ratio in patients with primary hypothyroidism (PHT) regarding the effect of levothyroxine (LT4) replacement therapy.The case-control study was conducted at the Department of Pharmacology, College of Medicine, Mustansiriya University, Baghdad, Iraq, from March to June, 2020 and involved 40 patients with primary hypothyroidism (PHT), including 20 newly diagnosed patients and 20 patients on levothyroxine (LT4) replacement therapy compared to 20 healthy controls. Anthropometric, lipid and pressure profiles were evaluated. Also T3, T4, TSH, NPY and AgRp serum level were estimated in different treated groups. SPSS version 20.00 was used for data analysis.Body mass index (BMI) was higher in the newly diagnosed patients without thyroxine therapy as compared to patients on thyroxine therapy (P=0.03). Blood pressure profile was higher in patients with PHT compared to the controls (P=0.0001). NPY serum level was lower in patients with PHT without thyroxine therapy (27.32±10.30ng/dL) as compared to patients with PHT on thyroxine therapy (61.10±22.78ng/dL), (P=0.04). AgRP serum level was lower in patients with PHT (9.81±4.86ng/dL) as compared to the patients on the thyroxine therapy (28.99±2.16ng/dL), (P=0.03). Besides, NPY-AgRP ratio (NAR) was higher in patients with PHT (2.78±0.14) as compared to patients with PHT on thyroxine therapy (2.10±0.19), (P=0.0001).Both of NPY and AgRP serum levels are reduced in the newly diagnosed patients with PHT and ameliorated following LT4 replacement therapy. Also NPY/AgRP ratio is linked with early PHT and regarded as a prognostic value for the outcomes of patients with PHT.

To elucidate the effect of metformin alone or in combination with sitagliptin on osteocalcin serum levels in obese patients with type 2 diabetes mellitus (T2DM).This case-control study was conducted at the Department of Clinical Pharmacology and Therapeutic, College of Medicine, Mustansiriyah University, Baghdad, Iraq, from February to April, 2019. This study comprised 62 obese T2DM patients compared with 28 healthy controls, they were divided into three groups; Group I: Obese patients with T2DM on metformin (n=36), Group II: Obese patients with T2DM on metformin plus sitagliptin (n=26), and Group III: healthy controls subjects (n=28). Body mass index (BMI), blood pressure profile, lipid profile, Glycaemic indices, and serum levels of human osteocalcin were measured. The data analysis was done by using SPSS 20.Osteocalcin serum level was lower in patients with T2DM compared with the control (P=0.001), also it was relatively low in metformin (MT) group (21.04±3.16 ng/mL) compared to sitagliptin (ST) group (25.65±7.30 ng/mL), (P=0.04). In relation to the HbA1c, osteocalcin serum level was reduced in patients with T2DM with high HbA1c (HbA1c-H) compared to the patients with T2DM with low HbA1c (HbA1c-L), (P=0.03) and was not significantly different when compared with moderate HbA1c (HbA1c-M), (P0.05). However, osteocalcin was negatively correlated with HOMA-IR(r=-0.78, P=0.0001).Osteocalcin serum level was reduced in T2DM patients and negatively correlated with HOMA-IR and HbA1c and FBG. Combination of metformin with sitagliptin was more effective than metformin monotherapy in amelioration of osteocalcin serum level in patients with T2DM.

Covid-19 is caused by a novel coronavirus named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 binds angiotensin converting enzyme 2 (ACE2), which is greatly expressed in different tissues including lung alveolar type II cells. Infection with SARS-CoV-2 triggers acute host immune response, inflammatory reactions and cytokine storm leading to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Different studies reported the pleiotropic effects of statins such as the anti-inflammatory and immune-modulatory effects via modulation of antigen presentation and adhesion of inflammatory molecules since; statins have potential anti-oxidant and redox balance effects that improve endothelial dysfunction and cardiovascular integrity. Objective of the present study is to verify the beneficial and harmful effects of statins in Covid-19. Statins upregulates ACE2 receptors and attenuates the down-regulation effect of SARS-CoV-2 on the ACE2 receptors. Consequently, reduction of ACE2 receptors augment the deleterious effect of angiotensin II (AngII) which causes vasoconstriction and initiation of ALI. On the other hand, statins therapy may increase risk of viral infections such as SARS-CoV-2 via lowering of low density lipoprotein (LDL) since; circulating LDL adhere and inactivates SARS-CoV-2. Statin therapy improves the outcomes of Covid-19 pneumonia through anti-inflammatory, immune-modulation, and in vitro anti-SARS-CoV-2 effects. The antiplatelet and antithrombotic effects may reduce Covid-19 induced-coagulopathy and progression of ARDS.

To assess the metabolic effects of primary hypothyroidism (PHT) on the leptin (LP), adiponectin (ADP) level and leptin adiponectin ratio (LAR), with identification of the beneficial effects of L-thyroxine (LT4) therapy on these parameters.This case-control study was conducted at the Department of Pharmacology, College of Medicine, Mustansiriyah University, Baghdad, Iraq, from July to October 2019. This study included 62 PHT patients, of whom 27 were newly diagnosed and 35 were on LT4 therapy. There were 28 healthy controls. Anthropometric, lipid and pressure profiles were evaluated along with estimation of TSH, T3, T4, LP and ADP serum levels. SPSS version 20.00 was used for data analysis.LP serum level did not significantly differ among the three groups (P=0.23), however, ADP serum level was higher in patients with PHT on LT4 therapy (77.48±9.97ng/dL) as compared to the newly diagnosed patients without LT4 (66.21±7.67ng/dL), and controls (71.40±10.72), (P=0.01). Moreover, LAR was higher in non-treated PHT (1.29±0.18) as compared to the controls (1.13±0.14), (95%CI=0.0568 to 0.2632, P=0.001) and treated PHT (1.04±0.16), (95%CI=-0.3480 to -0.1520, P=0.001). On the other hand, no significant difference was detected between healthy controls and treated PHT patients (95%CI=-0.1871 to 0.0071, P=0.07).PHT is associated with poor cardio-metabolic profile and high LAR. ADP but not LP, mainly affected in patients with PHT. However LAR is better than ADP and LP in reflecting the underlying PHT-induced cardio-metabolic derangements. LT4 replacement therapy improves cardio-metabolic profile, ADP and LP serum levels with significant amelioration of LAR in PHT patients.

The current systematic review was planned to illustrate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections during pregnancy and to explore pregnancy outcomes, vertical and perinatal transmission as well as management of coronavirus disease-2019 (Covid-19) during pregnancy.The multidisciplinary systematic review was conducted at the Department of Clinical Pharmacology and Therapeutic Medicine, Al-Mustansiriyah University, Bagdad, Iraq. The literature search was conducted in September 2021 and included databases as Medline, PubMed, Scopus, Web of Science, Cochrane Central Register of Controlled Trials and Science Direct databases related to articles on pregnancy and SARS-CoV-2 infections, published between December 2019 and July 2021.Of the 30 articles reviewed, 12(40%) were included. Major reasons for including a small number of studies in systematic review were that majority of the studies had insufficient description of study; analysis was duplicate across various publications, and inadequate explanation of impact of SARA-CoV-2 infection on the pregnancy outcomes. This review included 12 studies based on the assessment and estimation of risk of bias and quality of the eligible studies.Findings revealed that pregnant women were predominantly susceptible to the respiratory viral infection and severe pneumonia due to physiological immune-suppression, immune adaptation and pregnancy-induced changes. The clinical presentation and management of pregnant women with Covid-19 is similar to that of non-pregnant women and there is no strong clinical evidence of vertical transmission. Also, only chloroquine and remdesivir have been found to be effective in the treatment of Covid-19 during pregnancy.

To evaluate the effect of proton pump inhibitors on glycaemic indices in patients with type 2 diabetes mellitus.The case-control study was conducted at the National Diabetes Centre, Mustansiriyah University, Baghdad, Iraq, from January to April 2018, and comprised type 2 diabetes patients and non-diabetic healthy controls. The subjects were divided into three groups: Group A had controls on proton pump inhibitors; Group B had patients treated with metformin 850 g/day; and Group C had patients treated with metformin 850 g/day plus proton pump inhibitors. Gastrin serum levels, lipid profile, glycaemic indices and blood pressure changes were measured in the groups. Data was analysed using SPSS 20.Of the 100 subjects, 60(60%) were patients with a mean age of 54.98}4.22 years, while40(40%) were controls with a mean age of 50.69}4.34 years. Group A had 40(40%) subjects, while Group B and Group C had 30(30%) each. Proton pump inhibitors improved glycaemic indices and lipid profile in the patients 9p0.05) while increasing gastrin serum levels which were significantly correlated with reduction in glycated haemoglobin, fasting blood glucose and augmentation of β-cell function (p0.05 each).Proton pump inhibitors improved glycemic indices and metabolic profile in type 2 diabetes patients via augmentation of gastrin serum levels.