Chronic pain in chronic heart failure: a review article

Heart failure [HF] is one of the main causes of death and disability in the world. The prevalence of HF in developed countries is between 1% and 2% of the adult population and approximately between 6% and 10% in the elderly, giving rise to high costs of care and treatment. Indeed, in the United States, the direct and indirect costs exceeded 23 billion dollars in 2002. HF is typically characterized by periods of acute symptoms followed by returns to nearly asymptomatic periods. As dyspnea and fatigue are considered the signature symptoms of HF, other symptoms such as pain go unnoticed. Awareness of the burden of pain, however, is growing in patients with chronic HF. The past 2 decades have witnessed remarkable technical headway in cardiology and many patients have survived despite the progressive impairment of their cardiovascular function. It is, therefore, of great value to investigate the prevalence and management of pain in patients with HF. To that end, we undertook a comprehensive search using the MEDLINE database for studies and guidelines on the subject of pain and HF and the complications and considerations and finally selected 65 studies for review

effect of Migri-Heal on nitric oxide production in an in vitro inflammatory model of primary microglial cells

Background: Recently, much attention has been directed towards considering activated microgelial cells as putative targets for treatment of neurological disorders. MigriHeal as a novel herbal remedy was introduced for the treatment of migraine headaches. The previous researches has shown that MigriHea extracts can decrease NO in an in vitro inflammatory model. The aim of this study was to investigate the effect of MigriHeal on NO generation from LPS- stimulated microglia cells

Materials and Methods: Neonatal rat primary microglial cells were isolated from the mixed glial cultures and the purity of the cultures was determined by immunocytochemistry. Microglial cells were pretreated with Migri-Heal and activated by 1microg/ml LPS. Subsequently, NO levels in the culture supernatants were measured by a griess reaction. Our results showed that Migri-Heal 50microg/ml significantly reduced NO level in inflamed microglia in a dose-dependent manner

Results: The results showed that different concentrations of Migri-Heal had no prominent effect on cell viability in presence of LPS as compared with the control group. In addition, the pretreatment of microglia cells with Migri-Heal can prevent from a morphological changes of the cells into the round and phagocytic shape

Conclusion: Our study demonstrated that MigriHeal might have NO scavenging properties. Integrative studies are warranted to uncover the novel pharmacological insights of this herbal remedy as an putative therapeutic approach against diseases -associated with inflammation

evaluation of gene expression and enzyme activity of SIRT1 in peripheral blood mononuclear cells isolated from patients with relapsing-remitting multiple sclerosis

Background: Little in known regarding the clinical relevance of SIRT1 in multiple sclerosis [MS]. Here, we aimed to evaluate mRNA expression, protein level and enzyme activity of SIRT1 in peripheral blood mononuclear cells [PBMCs] isolated from relapsing -remitting MS patients [RRMS] and healthy controls

Materials and Methods: Twenty patients with RR-MS and twenty two age- and sex-matched healthy subjects were enrolled in this case-control study. Following PBMCs isolation, mRNA expression was evaluated by real time-PCR. SIRT1 activity and SIRT1 protein level were measured using a fluorometric assay and an enzyme-linked immunosorbent assay [ELISA] respectively, in PBMC lysates

Results: There was no statistically significant difference in the mRNA expression of SIRT1 [p=0.56] and its protein levels [p=0.15] between MS patients and healthy subjects. By contrast, SIRT1 enzyme activity were significantly [p=0.008] lower in RRMS patients compared with that in healthy subjects

Conclusion: Our findings demonstrated that enzyme activity of SIRT1 is significantly lower in PBMCs of RRMS patients in comparison with healthy subjects. However, more investigations are essential to clarify the role of SIRT1 in MS pathogenesis.Keywords: enzyme activity, multiple sclerosis, pathogenesis

Expression and enzyme activity of MnSOD and catalase in peripheral blood mononuclear cells isolated from multiple sclerosis patients

Background: it is evident that oxidative stress plays a crucial role in etiology of multiple sclerosis [MS]. Dysregulation of antioxidant enzymes have been implicated in demylination and neuronal loss in MS. The aim of this study was to evaluate mRNA expression and activity of manganese superoxide dismutase [MnSOD], and catalase in peripheral blood mononuclear cells [PBMCs] from patients with relapsing-remitting multiple sclerosis [RRMS] and healthy controls

Materials and Methods: we recruited 20 RRMS patients and 20 age-and sexmatched healthy subjects. PBMCs were isolated, RNA was extracted and real time-PCR was used to evaluate mRNA expression of MnSOD and catalase. Enzyme activity of MnSOD and catalase were measured using colorimetric assays

Results: we found a significant increase in mRNA expression and activity of catalase in PBMCs from patients compared with controls, which was accompanied by reduced activity and expression of MnSOD in MS patients

Conclusion: it appears that impaired antioxidant enzymes in term of high activity of catalase and decreased activity of MnSOD are involved in MS pathogenesis, however further studies are needed to establish this concept

MTHFR Gene polymorphisms and susceptibility to Migraine Attacks

Background: Migraine consisting of migraine with aura [MA] and migraine without aura [MO] is a painful neurovascular disorder affecting approximately 16% of the general population. A combination of genetic and environmental factors is involved in the pathogenesis of migraine. The MTHFR enzyme is involved in homocysteine [Hcy] metabolism and it has been reported that 1298 A to C and 677 C to T mutations in the MTHFR gene are associated with an increased in plasma Hcy levels. Hcy is a highly reactive amino acid and causes endothelial injury. Because a plausible theory about vascular impairment in migraine, it is considered that mutations in MTHFR gene and folate metabolism are associated with migraine

Materials and Methods: in total, 75 patients with migraine [24 with MA and 51with MO] in accordance with the IHS criteria participated in this case-control study. Control group were 128 normal matched healthy subjecys who selected from same region without history of migraine or other neurologic disorder after interviewing and examining by a physician. Mean age at entry was 36.42+/-9.6 and 31.64+/-8.9 years old in migraine and control group respectively. MTHFR polymorphisms were investigated by PCR-RFLP

Results: genotypic results indicated that the prevalence of the MTHFR 677TT genotype in migraine subjects was higher than control [17.3% and 3.1% respectively, P<0.001]. Interestingly the risk of migraine was 6-fold higher in subjects possessing the MTHFR 677T homozygous variant [OR=6.5; CI95%: 2.03-20.76]. No significant difference in the prevalence of MTHFR A1298C genotypes was observed in migraine group when compared to controls [P>0.001]

Conclusion: it seems that MTHFR C677T is a potential genetic risk factor for migraine attacks, both in MA and MO subclasses in Iranian population. C677T and A1298C joint effect could amplify the potential influence of each SNPs

Snake bite

Snake bites are increasing amongst those who unlawfully keep snakes as pets worldwide. The rural population active in agricultural works, laborers, herders, professional snake h and lers, trekkers, snake charmers and fishermen are at risk for snake bites. Objectives: To determine the frequency and pattern of vasculotoxic effects in patients with snake bite. Design: Case Study. Period: Six Months Setting: Liaquat University Hospital Hyderabad. Patients and methods: All the patients who initially present in casualty department of hospital with the history of snake bite were enrolled in the study. The vasculotoxic effects were evaluated by whole blood clotting time [WBCT] test, bleeding time, PT/APTT, hypofibrinogemia, DIC and thrombocytopenia. Relevant information would be entered in specifically designed proforma for this study. The data was entered, saved and analyzed in SPSS. So no test of significance would be applied. Results: Out of 140 patients 112[80%] had vasculotoxic effects, of which 80[72%] were males and 32[28%] were females. The mean age +/-SD of the overall patients was 37.53+/-8.72 whereas the mean age +/-SD of male and female population was 38.98+/-7.44 and 34.88+/-4.32 respectively. The systemic bleeding was observed in 99% patients, the fang marks in 94 patients, the prolonged bleeding time, WBCT and PT/APTT in 103, 96 and 101 patients, thrombocytopenia in 93 patients, hypofibrinogemia in 81 patients and DIC in 76 patients. The hamaturia [22%], hamoptysis[16%] and hametemesis [11%] was predominant features. The gangrene was observed in 02 patients, vomiting was observed in 60% of patients had haematemesis in 11%, bleeding gums in 03 cases and haemoptysis in 16%. Renal failure was observed in 12 cases. Conclusions: The coagulation tests disturbed as venom increases the clotting time. Proteins digesting enzymes or thrombin like activity of venom may be one of the causes for prolongation coagulation tests [vasculotoxic effects]

[Teratogenic effects of Origanum Vulgare in mice fetals]

A number of studies on reproduction have mentioned Origanum Vulgare extract's ability to reduce mortality rates and improve fertility rates. However, other studies have suggested that it is possible to use Origanum Vulgare extract to induce abortion. The aim of this study was to investigate the effect of different doses of Origanum Vulgare on embryo survival and macroscopic abnormalities in mice. In this study, 24 mice Balb/c female weighting approximately 25-30 g were divided into 4 groups. Origanum Vulgare extract was prepared; different concentrations [2.5, 12.5, and 25 mg in 0.25 ml distilled water] were administered, by oral gavage, to three experimental groups of mice between day 6 [starting gastrulation] until day 15 of pregnancy [end of organogenesis]. The control group consisted of six mice that received 0.25 ml of distilled water daily. On day 16 of study, pregnant mice were anesthetized by chloroform and fetuses were removed and stained with Alcian Blue, Alizarin Red s and microwave irradiation. Morphological and skeletal abnormalities were investigated by light and stereomicroscopes. The results of this study showed that high doses of the Origanum Vulgare extract significantly decreased the mean number of embryos [10 +/- 0.5, P>0.05], mean number of live embryos [7 +/- 0.5, P>0.05] in each mouse and resulted in significant reduction in mean weight[1184 +/- 8 mg, P>0.05] and crown-rump length[11.9 +/- 0.23 mm, P>0.05] and the overall size of fetuses compared to control group, whereas there was no significant difference between the groups receiving low dose of Origanum Vulgare extract with control group. In addition, under the effect of the Origanum Vulgare extract the subcutaneous bleeding seemed [2 +/- 0.1, P>0.05] significantly more frequent compared to the control group. Origanum Vulgare extract did not have any positive effect on fetal development; and high dosages led to an increased incidence rate of abortion and fetal malformations in the fetuses of women who received it.

effect of macromolecule source and type of media during in vitro maturation of sheep oocytes on subsequent embryo development

Oocyte maturation and subsequent in vitro production [IVP] of embryos are affected by diverse groups of chemicals in maturation medium which are needed for successful mammalian oocyte maturation during which the dramatic cytoplasmic and nuclear reprogramming events take place. This study was designed to evaluate the effects of protein source [fetal bovine serum, FBS, and bovine serum albumin, BSA] as well as two different maturation media during in vitro maturation of ovine oocytes on subsequent embryo development. Cumulus oocyte complexes were recovered from ovaries obtained from slaughter house and cultured for 24 hr in either TCM-199 or SOFaa maturation medium supplemented with 10% [v/v] FBS or 0.8% [w/v] BSA. Data were analyzed by one-way ANOVA using Sigma Stat [Ver. 2]. A p-value smaller than 0.05 was considered statistically significant. The proportions of cleavage and total blastocyst [evaluated on days 3 and 6, respectively] were significantly higher in FBS than BSA supplemented groups, though no differences were observed between the two used different maturation media. The cryotolerance of blastocysts was negatively influenced by the presence of FBS rather than BSA during IVM. The quality of produced embryos, however, was affected neither by the source of macromolecules nor the maturation medium in terms of hatching rate, total blastocyst cells and inner cell mass/total cell ratio. The rate of oocyte development was improved by the presence of FBS, though the cryosurvival of resulting blastocysts was negatively influenced by the presence of the serum during in vitro production of sheep oocytes

Unusual presentation of organic foreign body in upper aerodigastric tract: report of two cases

Foreign body ingestion is one of the leading causes of pediatric accidents. Delayed presentations of organic foreign body are usually surprising due to their ability to stick, swell and obstruct the lumen. Obstruction of upper aerodigastric tract due to seeds after one week of aspiration resembling esophageal stricture or lobar pneumonia is

[Analysis of HLA-G transcripts in PBMCs of normal and lupus individuals and effect of IFN-gamma on the expression of HLA-G]

HLA-G is a nonclassical major histocompatibility complex antigen and is expressed as seven isoforms, including four membrane bound [HLA-G1 to-G4] and three soluble [HLA-G5 to-G7] forms. The pattern of selective expression of HLA-G transcripts in tissues shows the existence of a tight transcriptional control on the gene expression. It has been revealed that cytokines including interfrons and IL-10 could cause stimulation of the HLA-G transcription. The purpose of this study was to examine the effects of IFN-gamma on the expression of HLA-G transcripts in both PBMCs of normal and SLE patients. Whole blood of 20 female SLE patients and 15 healthy donor candidates for Bone Marrow Transplantation were used. PBMCs were isolated from the whole blood by Ficoll gradient centrifugation and cultured with or without IFN-gamma /LPS for 48 hours. Total RNA was extracted from the cells by trizol method. After reverse transcription of RNA to cDNA and the performance of a multiplex PCR for beta actin and HLA-G, the PCR products were analyzed using electrophoresis on a 2% agarose gel and stained with ethidium bromide. The results showed that the transcription of HLA-G was higher in SLE patients compared to normal controls. Addition of IFN-gamma /LPS could influence the expression of this molecule by increasing the transcription of HLA-G in both normal and patient PBMCs [P?0.05]. Transcription of HLA-G gene could be increased by the cytokine IFN-gamma. This observation is in accordance with previous reports. This effect could be assigned to both normal and lupus Patients. The effects of the cytokine IFN-gamma /LPS in the induction of HLA-G transcription were higher in normal than lupus patients. Nevertheless, the total expression of HLA-G was higher in lupus patients

Induction of liver metallothionein contribute to the developmental toxicity of valproic acid in rat

There is an increased risk of neural tube defects and axial skeletal malformations among infants born by mothers who had received valproic acid. The aim of the present study is, if administration of valproic acid can induce maternal hepatic Metallothionein [MT] synthesis and so secondary decrease of plasma Zn. In the present experimental study, mated rats were divided into four groups of 12 animals each [control, valproic acid [VPA], valproic acid + zinc [VPA+ Zn] and Zinc [Zn] groups. The VPA group received 300 mg/kg valproic acid; daily. The control group received an equal volume of 0.9% NaCI. The VPA+ Zn group received 300 mg/kg VPA as well as 30 mg/kg zinc sulfate, and the Zn group received 30 mg/kg zinc sulfate, daily. These drugs were administered intraperitoneally from day 6 through day 15 of gestation. Dams were killed on GD 16 or 20. Blood was drawn to determine plasma zinc; furthermore, maternal liver Zn and MT were also determined. The zinc concentration in the plasma of rats treated with valproic acid was significantly lower than those of the other groups on GD 16 [p=0.004], but liver Zn [p=0.016] and MT [p=0.004] were significantly higher than those of the control group. On GD 20 the incidence of skeletal malformations and neural tube defects tended to be higher in VPA group than VPA+ Zn treated group and no anomalies were seen in the control group. The results from the present experiment support hypothesis that one of biochemical lesions causing the teratogenicity of VPA is a drug -induced maternal plasma zinc deficiency secondary to Metallothionein induction in liver

Comparison of nitric oxide concentration in seminal fluid between infertile patients with and without varicocele and normal fertile men

Elevated nitric oxide [NO] levels have been shown to have toxic effects on sperm function and motility. This study was conducted to compare NO levels in the seminal fluid of infertile men with varicocele with those of infertile and fertile men without varicocele. Semen samples were obtained from 40 infertile men with varicocele [group 1], 40 infertile men without varicocele [group 2], and 40 fertile volunteers without varicocele [group 3]. NO levels in the seminal plasma of patients in each group were measured and compared. In infertile men with varicocele, semen parameters, including sperm count and motility, and grade of varicocele were also determined. Mean NO concentrations were 52.34 +/- 26.62 micro mol/L, 37.06 +/- 20.39 micro mol/L, and 33.7 +/- 18.99 micro mol/L in groups 1, 2, 3, respectively. Concentrations in group 1 were significantly higher than those in groups 2 and 3 [P=0.001]. In group 1, no significant correlations were seen between NO concentrations and grades of varicocele, sperm count, sperm motility, or ages of the patients. Data from the current study suggest a possible role of NO in damaging the sperm function in varicocele as demonstrated by an increased concentration of NO in the seminal fluid of infertile men with varicocele compared with the seminal fluid of fertile and infertile men without varicocele

Sedative and analgesic efficacy of Barshasha in surgical patients

Placebo controlled doubled blind study on 64 patients of cholelithiasis to assess the sedative and analgesic efficacy of Barshasha in pre-operative period. The drug was able to increase the duration of sleep and rate pressure product showed a declining trend in pre-operative period. Pre-operatively oral secretions were significantly decreased but no significant alteration was found in cardiovascular parameters. In post-operative period, demand for analgesic was significantly less

Late repair of the tendon achilles

The results of untreated ruptures of the tendon achilles are widely accepted as poor. Surgical or conservative treatment is fruitful in ruptures presenting early, but in ruptures presenting late only surgical treatment is possible because the proximal end of the tendon retracts. A prospective and retrospective study of 5 patients of Late Repair of the Tendon Achilles was carried out at Liaquat Medical College Hospital, Jamshoro / Hyderabad from July 1996 to June 1998. The average age for the series was 43 years. Sex incidence finale to female ratio was 4:1 patients. Delay between injury and time of operation had been from one month to an year. All cases were operated upon. Direct suturing method was used. Follow up of the patient varied from 4 months to 12 months. The results shown by direct Suturing in the Achilles tendon is comparable to any other form of treatment