Phytochemicals That Act on Synaptic Plasticity as Potential Prophylaxis against Stress-Induced Depressive Disorder

Depression is a neuropsychiatric disorder associated with persistent stress and disruption of neuronal function. Persistent stress causes neuronal atrophy, including loss of synapses and reduced size of the hippocampus and prefrontal cortex. These alterations are associated with neural dysfunction, including mood disturbances, cognitive impairment, and behavioral changes. Synaptic plasticity is the fundamental function of neural networks in response to various stimuli and acts by reorganizing neuronal structure, function, and connections from the molecular to the behavioral level. In this review, we describe the alterations in synaptic plasticity as underlying pathological mechanisms for depression in animal models and humans. We further elaborate on the significance of phytochemicals as bioactive agents that can positively modulate stress-induced, aberrant synaptic activity. Bioactive agents, including flavonoids, terpenes, saponins, and lignans, have been reported to upregulate brain-derived neurotrophic factor expression and release, suppress neuronal loss, and activate the relevant signaling pathways, including TrkB, ERK, Akt, and mTOR pathways, resulting in increased spine maturation and synaptic numbers in the neuronal cells and in the brains of stressed animals. In clinical trials, phytochemical usage is regarded as safe and well-tolerated for suppressing stress-related parameters in patients with depression. Thus, intake of phytochemicals with safe and active effects on synaptic plasticity may be a strategy for preventing neuronal damage and alleviating depression in a stressful life.

Frequency of hepatitis B and C in young asymptomatic males

To understand the latest trends of hepatitis B and C viruses frequency by detecting Hepatitis B surface antigen and hepatitis C antibodies in young asymptomatic males. Descriptive study. This study has been carried out at the Department of Pathology Combined Military Hospital, Risalpur and Department of Virology, Armed Forces Institute of Pathology, Rawalpindi from 1st March 2010 to 30th September 2010. One thousand and forty two physically fit candidates between 17 to 23 years of age, reporting to Engineer Centre Risalpur, from Punjab and Khyber Pakhtunkhwa for induction in Armed Forces, were enrolled in the study by non-probability convenience sampling. They were screened for HBsAg and anti HCV by Immuno-chromatographic rapid test devices, at Pathology Department Combined Military Hospital Risalpur. All positive samples were confirmed from Department of Virology, Armed Forces Institute of Pathology Rawalpindi by Enzyme Linked Immuno-sorbent assay. Out of 1042 study subjects, screened during the period, 31 [2.97%] were found to be positive for HBsAg and 16 [1.53%] for anti HCV. As per available information, 876 study subjects belonged to rural areas and 166 belonged to urban areas. Mean age was 20 +/- 1.4 years and range was 17 to 23 years. Province wise 987 individuals belonged to Punjab, out of which 30 cases [3.0%] were positive for HBsAg and 15 cases [1.5%] were positive for anti HCV, which indicates that the predominant part of the study subjects were from Punjab and their positivity percentage is almost same as given in the study, whereas 55 individuals belonged to Khyber Pakhtunkhwa. Frequency of Hepatitis B and C in asymptomatic young males of Punjab is 3% and 1.5% respectively and that for Khyber Pakhtunkhwa is 1.8% for both viruses

Correlation of axillary temperature with rectal temperature in clinically unstable neonates

To test the hypothesis that axillary temperature may not correlate well with rectal temperature in unstable neonates and to compare the predictive value of axillary temperature recording in unstable neonates with that of healthy neonates. This cross-sectional and analytical study. Neonates from birth till the age of one month were included in the study. Axillary temperature and rectal temperature were recorded upon arrival to the unit, using digital thermometers. At arrival, 109 neonates were categorized as stable and 117 as unstable. There were no statistically significant differences in their demographic data such as gender, gestational age, postnatal age and weight of the neonates in the two groups. Over all mean axillary temperature was 97.02°F [SD +/- 2.5] and mean rectal temperature was 97.99°F [SD +/- 2.21]. The overall correlation between the axillary and rectal temperature was 0.632 [p<0.001]. A significant difference [P-value <0.001] in the Pearson correlation [r] between axillary and rectal temperature recording in the two groups was found. A significant difference was also observed in regression lines between the two groups. Axillary temperature measurement is not a reliable method of documenting the arrival temperature in clinically unstable neonates

Pattern and outcome of admissions to neonatal unit of Khyber teaching hospital, Peshawar

To determine the number, disease pattern and outcome of admitted patients to neonatal unit. Khyber Teaching Hospital, Peshawar N.W.F.P from 1st Jan, 2005 to 31st Dec, 2005. Data of all the neonatal admissions was recorded and analyzed for age, weight at the time of admission, sex, reason for admission, duration of hospital stay and final outcome of these patients. Their referral source was also determined. A total of 1694 neonates were admitted during the year 2005. Among them male were 1219[71.96%] and females were 475 [28.04%]. Maximum number of patients was admitted during 1st 24 hours of life. Majority 1056 [62.33%] were referred from hospitals and maternity homes along with 458 [27.03%] home deliveries. Low birth weight accounted for 41.20% of total admissions. Neonatal infections were the next commonest cause of neonatal admissions which includes sepsis [26.03%], pneumonia [1.71%] and Meningitis [1.18%], premature babies [26.50%], N.N.J [19.95%], and birth asphyxia [16.52%]. Other causes of neonatal admission were congenital heart disease [1.41%], meconium aspiration syndrome [1.18%], I.U.G.R [0.82%] and R.D.S [0.59%]. Among total admissions 1212 [71.54%] were sent home after their complete recovery, 252 [14.87%] expired, left against medical advise [L.A.M.A] 120 [7.08%] and discharged on their attendants request 107 [6.31%]. Pre-maturity, neonatal infection, neonatal jaundice and birth asphyxia were the main causes of neonatal admissions. Increased awareness for in time referral to tertiary level hospitals is mandatory by those health workers who conduct deliveries at private hospital /maternity homes as well as those who conduct deliveries at homes

Frequency of cytogentic abnormalities in patients of Acute Myeloid Leukaemia

Cytogenetic analysis performed at diagnosis is considered to be the most valuable prognostic factor in acute myeloid leukaemia [AML]. Cytogenetic abnormalities which indicate a good prognosis include t[8; 21], inv[16] and t[15;17]. Normal cytogenetics carries average risk in AML. Patients with AML that is characterized by deletions of the long arms or monosomies of chromosome 5 or 7 or by abnormalities of 11q23 have particularly poor prognosis. To determine the frequency and type of cytogenetic abnormalities in Pakistani patients of AML. Design: Descriptive study. Subjects and Thirty six patients of acute myeloid leukaemia were referred to the department of Heamatology, Armed Forces Institute of Pathology, Rawalpindi for cytogenetic studies during the period from March 2001 to September 2004. Five ml of venous blood was collected by venesection in vacutainer containing sodium heparin as anticoagulant. Blood was cultured on RPMI-1640 medium enriched with L-glutamine and foetal bovine serum. Phytohaemagglutin was used as T-cell mitogen. The cultures were incubated for 72 hours at 37°C. Mitoses were arrested in metaphases by colchicine. The cells were harvested and slides were made. Slides were aged and trypsin digestion was done. Slides were stained with Giemsa stain. Twenty metaphases were analysed under the microscope and the observations were recorded. In 10 patients' culture failed to yield evaluable metaphases. Out of 26 evaluated patients, cytogenetic abnormalities carrying good prognosis were seen in 6[23%] patients t[8;21] in 3 cases, t[15;17] in 2 and inv[16] in one patient. Normal karyotype carrying standard risk was seen in 17[65.4%] patients. Whereas abnormalities carrying poor prognosis were seen in only 3[11.6%] patients. These comprised 2 cases of trisomy 8 and one of dup [3][q21; q26]. This study reveals that majority of Pakistani patients with AML belong to good [23%] or standard [65.4%] risk groups. Only 11.6% patients belong to poor risk group

Frequency of HLA DR2 in patients with severe and very severe Aplastic anaemia

To determine the frequency of HLA DR2 in Pakistani patients with severe and very severe aplastic anaemia. Introduction: In many cases aplastic anaemia is mediated by the immune mechanisms. Increased frequency of certain HLA haplotypes in patients with autoimmune diseases have led to the investigation of HLA subtypes in aplastic anaemia. HLA DR2 was found to be the most frequently encountered allele in aplastic anaemia. It has been reported that patients of aplastic anaemia, who possess HLA DR2 show a good response to immunosuppressive treatment. This study has been designed to establish frequency of HLA DR2 in patients of aplastic anaemia in our population. Setting: Armed Forces Institute of Pathology and Armed Forces Bone Marrow Transplant Centre, Rawalpindi-Pakistan. Materials and Fifty two cases of aplastic anaemia diagnosed at AFIP/AFBMTC during last 03 years [March 2001 to December 2003] were included in the study. Laboratory investigations to establish the diagnosis included blood complete picture, reticulocyte count, bone marrow aspiration and bone marrow trephine biopsy. Cytogenetic studies were carried out in selected cases to exclude possibility of hypoplastic myelodysplastic syndrome/Fanconi's anaemia. LAP score, ham's test, sucrose lysis test, urine for haemosiderin and CD59 analysis were carried out in suspected cases to exclude paroxysmal nocturnal haemoglobinuria. All cases were tested for HLA DR2 by standard National Institute of Health two stage microlymphocytotoxicity assay. Out of 52 patients, 35 were males and 17 were females [M: F 2:1]. Median age of the patients was 17 years [3-35 years]. Twenty eight [54%] of the patients were of severe aplastic anaemia and 24 [46%] were of very severe aplastic anaemia. HLA DR2 was positive in 31[60%] patients compared to 4,1% in healthy population [p. 0.007]. An increased frequency of HLA DR2 is also seen in Pakistani patients of aplastic anaemia which is associated with a good response to immunosuppressive therapy

Graft versus host disease in allogeneic stem cell transplantation - 3 l/2 years experience

To evaluate the frequency and outcome of graft versus host disease after allogeneic stem cell transplant in haematological disorders at Armed Forces Bone Marrow Transplant Centre, Rawalpindi from July 2001 to December 2004. Eighty-six patients with various haematological disorders namely aplastic anaemia [n=32], b-Thalassaemia [n=25], CML [n=22] ALL [n=3], AML [n=l] Fanconi's anaemia [n=2], and Gaucher's disease [n=l], underwent allogeneic stem cell transplantation. All patients received cyclosoprin, prednisolone and short course of methotrexate as GvHD prophylaxis. The patients who developed acute GvHD > grade-II or chronic extensive GvHD received steroids at a starting dose of 2 mg/kg body weight along with gradual increase in cyclosporine dosage [max dose 12.5 mg/kg]. The overall incidence of acute GvHD grade-II to IV was 44.2% [n=38/86] where as the incidence of chronic extensive GvHD was 14% [n=12/86]. Acute GvHD was 68% [n=17/25] in B-Thalassaemia, 50% [n=ll/22] in CML, 50% [n=2/4] in Acute Leukaemias and 25% [n=8/32] in Aplastic Anaemia. Chronic GvHD was 25% [n=l/4] in Acute Leukaemias, 18.8% [n=6/32] in Aplastic Anaemia, 18.2% [n=4/22] in CML and 4% [n=l/25] in B-Thalassaemia. The overall survival in acute GvHD was 84.2% [n=32] where as the overall survival in chronic GvHD was 50% [n=6]. The overall mortality in acute GvHD was 15.8% [n=6] and 50% in chronic GvHD [n=6]. The morbidity and mortality due to severe acute and chronic GvHD remains high despite standard prophylaxis against GvHD. New strategies are needed to prevent and treat GvHD

Graft versus host disease in allogeneic stem cell transplantation - 3 1/2 years experience

To evaluate the frequency and outcome of graft versus host disease after allogeneic stem cell transplant in haematological disorders at Armed Forces Bone Marrow Transplant Centre, Rawalpindi from July 2001 to December 2004. Eighty-six patients with various haematological disorders namely aplastic anaemia [n=32], b-Thalassaemia [n=25], CML [n=22], ALL [n=3], AML [n=1] Fanconi's anaemia [n=2], and Gaucher's disease [n=1], underwent allogeneic stem cell transplantation. All patients received cyclosoprin, prednisolone and short course of methotrexate as GvHD prophylaxis. The patients who developed acute GvHD > grade-II or chronic extensive GvHD received steroids at a starting dose of 2 mg/kg body weight along with gradual increase in cyclosporine dosage [max dose 12.5 mg/kg]. The overall incidence of acute GvHD grade-II to IV was 44.2% [n=38/86] where as the incidence of chronic extensive GvHD was 14% [n=12/86]. Acute GvHD was 68% [n=17/25] in

Allogeneic stem cell transplantation in chronic myeloid leukaemia 2 1/2 year experience

To evaluate out come of allogeneic Stem Cell Transplantation [SCT] in chronic myeloid leukaemia [CMC] at Armed Forces Bone Marrow Transplant Centre, Rawalpindi from April 2002 to October 2004. Twenty-two patients with CML underwent allogeneic SCT from HLA matched siblings. Patients were divided into standard [n=14] and high-risk [n=8] groups. Patients were subjected to conditioning regimens consisting of Busulphan and Cyclophosphamide. Cyclosporin, Prednisolone and Methotrexate were given for GvHD prophylaxis. All donors were subjected to PBSC harvest after G-CSF therapy for five days. All received G-CSF from Day+5 until ANC >0.5 x 109/l. The median age of the patients was 29 years [range 7-53 years] with a male to female ratio of 6.3:1. Engraftment was achieved in all patients. Median time to achieve neutrophil [ANC 0.5x109/l] and platelet [20x109/l] recovery was 13 days and 12 days respectively. Median stay in hospital was 18 days. Acute GvHD [Grade-II-IV] was observed in eleven patients [50%] while chronic GvHD was seen in four patients [18%]. One patient relapsed 8 months post transplant. Two patients [9%] developed Veno-occlusive disease [VOD] liver. One patient had haemorrhagic cystitis. Four patients [18%] had post transplant infectious complications, which included pseudomonas septicemia, aspergillosis, tuberculous pleural effusion and herpes zoster. Overall mortality was 22.7% [n=5]. The major causes of mortality were VOD liver, GvHD grade IV, Pseudomonas septicaemia and aspergillosis. Overall survival was 77.2% [n=17] and disease free survival was [n=16] 72.7%. Follow up ranges were from 23 to 828 days [median 212 days]. The preliminary results of SCT in this small series of patients with CML are very encouraging. To improve the long-term survival it is imperative that patients are transplanted early after diagnosis and conditioning regimens are selected carefully

FLAG-IDA in the treatment of refractory/ relapsed acute leukaemias: Single center study

To evaluate the efficacy and toxicity profile of the combination of fludarabine, high dose cytarabine, idarubicin, and granulocyte colony stimulating factor in refractory relapsed cases of acute leukaemia, a study is being conducted at Armed Forces Bone Marrow Transplant Centre [AFBMTC] Rawalpindi since January 2003. Data up to June 2004 [early report] is being presented. Twelve Patients with refractory/relapsed [Ref/Rel] acute leukaemia [AL] were treated with fludarabine 30mg/m2 and cytosine arabinoside [AraC] Arac 2 g/m2 for 5 days, idarubicin 10mg/m2 for 3 days, and granulocyte colony stimulating factor G-CSF 5 micro g/kg from day 0 till neutrophil recovery [ANC >1.0 x 109/l]. Response was evaluated by bone marrow examination on day 20-post chemotherapy. Patients included were refractory acute lymphoblastic leukaemia [ALL] [n=2], relapsed ALL [n=3], refractory acute myeloid leukaemia [AML] [n=3], secondary AML [n=2] relapsed AML [n=1] and acute undifferentiated leukaemia [AUL] [n=1]. Complete remission [CR] was achieved in 8 [66.6%] patients. Three [25%] patients died of post chemotherapy complications and one patient failed to achieve remission. Out of 8 patients who achieved CR, 4 underwent allogeneic bone marrow transfusion [BMT], 1 is being evaluated for the same, 1 received idorubicin, AraC and etopuside [ICE] and high dose AraC, 1 did not receive further chemotherapy and 1 relapsed two months after remission. Seven patients are still in CR after a median follow up of 8 months [range 3-18]. Major complications encountered were diarrhoea, mucositis, toxic ileus, transient hepatic toxicity, fungal and bacterial infections. In our experience, FLAG-IDA is well tolerated and effective regimen in relapsed / refractory acute leukaemias. The toxicity is acceptable, enabling most patients to receive further treatment, including transplantation procedures