Human amniotic epithelial cells (HAECS); a potential cell type for the hepatic disorders.

OBJECTIVE: To isolate a homogenous population of human amniotic epithelial cells (hAECs) from the amniotic membrane of the human placenta and differentiate them into hepatic-like cells with the help of small molecules. METHODS: hAECs were isolated by using the enzymatic digestion method and characterized for the presence of specific stem cell markers. In-vitro, hepatic differentiation of hAECs was carried out by using a combination of small molecules. Differentiated cells were observed under a live cell imaging microscope for morphological changes followed by gene and protein expression analysis by qPCR and immunocytochemistry respectively. RESULTS: The isolated hAECs attained characteristic cuboid epithelial shape and express stem cells marker. The hepatic differentiation method was optimized based on soluble chemical compounds supplied in the culture medium. The differentiated hAECs phenotypically acquire hepatic-like cell features and expressed hepatic markers as well as hepatic protein albumin at immature levels. CONCLUSIONS: The isolated population of hAECs is highly proliferative. Moreover, hepatic markers expression in the isolated hAECs makes them an exclusive source for the treatment of chronic liver diseases.

Loss of Function Variants in the XPC Causes Severe Xeroderma Pigmentosum in Three Large Consanguineous Families.

BACKGROUND: Xeroderma pigmentosum (XP) is a rare recessively inherited disorder that presents clinical and genetic heterogeneity. Mutations in eight genes, of which seven are involved in nucleotide excision repair (NER) pathway have been reported to cause the XP. METHODS AND RESULTS: Three large consanguineous families of Pakistani origin displaying typical clinical hallmarks of XP were evaluated at clinical and molecular level. Homozygosity mapping using microsatellite markers established linkage of the families to XPC gene on chromosome 3p25.1. Sanger sequencing of the XPC gene identified a novel homozygous single bp deletion [NM_004628.5; c.1934del; p.(Pro645Leufs*5)] and two previously reported mutations that included a nonsense [c.1243 C>T; p.(Arg415*)] and a splice acceptor site (c.2251-1 G>C), all segregating with the disease phenotypes in the families. CONCLUSION: This report has extended the spectrum of mutations in the XPC gene and will also facilitate in diagnosis of XP and counselling of families inheriting it, which is the only inevitable tool for preventing the disease occurrence in future generations.

Tetra-primers ARMS-PCR Based Association Analyses of Synonymous and Intronic Variants in the ADAM12 Gene with Susceptibility to Knee Osteoarthritis: A Case-Control Study.

Genetic variations in a disintegrin and metalloprotease 12 (ADAM12) gene may contribute to develop Osteoarthritis (OA) that is characterized by cartilage matrix degradation and osteophytes formation. Therefore, the aim of present study was to analyze the association between the ADAM12 gene variants and knee OA predisposition. Tetra-primers ARMS-PCR was employed, to genotype the ADAM12 gene polymorphisms (rs1044122 and rs1871054) in 400 knee OA patients and equal number of age-matched controls. The association between ADAM12 gene variants and OA susceptibility was estimated using the Chi-square, logistic regression, haplotypes and linkage analyses. A significant association of rs1044122 (genotype: χ2 = 18.94; P < 0.001, allele: χ2 = 19.10; P < 0.001) and rs1871054 (genotype: χ2 = 10.04; P = 0.007, allele: χ2 = 10.57; P = 0.001) was observed with increased OA susceptibility. The variant genotype of rs1044122 increased OA risk more than twice [odds ratio (OR) 2.20; P = 0.001] and the risk was higher in females (OR 2.43; P = 0.001). The variant genotype of rs1871054 was perceived to almost double the risk in females (OR 1.97; P = 0.003). Moreover, a significant association of rs1044122 and rs1871054 under the additive genetic model (P < 0.001 and P = 0.002, respectively) was observed. The targeted ADAM12 gene polymorphisms, showed significant association with knee OA susceptibility. Females harboring the polymorphisms might be at risk. Besides, the haplotype CC of rs1044122 and rs1871054 in the ADAM12 gene may double knee OA risk. These findings may help in determining the etiology of OA and recognizing the people at risk of developing knee OA.

Synthesis of Silver Nano Particles Using Myricetin and the In-Vitro Assessment of Anti-Colorectal Cancer Activity: In-Silico Integration.

The creation of novel anticancer treatments for a variety of human illnesses, including different malignancies and dangerous microbes, also potentially depends on nanoparticles including silver. Recently, it has been successful to biologically synthesize metal nanoparticles using plant extracts. The natural flavonoid 3,3', 4', 5,5', and 7 hexahydroxyflavon (myricetin) has anticancer properties. There is not much known about the regulatory effects of myricetin on the possible cell fate-determination mechanisms (such as apoptosis/proliferation) in colorectal cancer. Because the majority of investigations related to the anticancer activity of myricetin have dominantly focused on the enhancement of tumor cell uncontrolled growth (i.e., apoptosis). Thus, we have decided to explore the potential myricetin interactors and the associated biological functions by using an in-silico approach. Then, we focused on the main goal of the work which involved the synthesis of silver nanoparticles and the labeling of myricetin with it. The synthesized silver nanoparticles were examined using UV-visible spectroscopy, dynamic light scattering spectroscopy, Fourier transform infrared spectroscopy, and scanning electron microscopy. In this study, we have investigated the effects of myricetin on colorectal cancer where numerous techniques were used to show myricetin's effect on colon cancer cells. Transmission Electron Microscopy was employed to monitor morphological changes. Furthermore, we have combined the results of the colorectal cancer gene expression dataset with those of the myricetin interactors and pathways. Based on the results, we conclude that myricetin is able to efficiently kill human colorectal cancer cell lines. Since, it shares important biological roles and possible route components and this myricetin may be a promising herbal treatment for colorectal cancer as per an in-silico analysis of the TCGA dataset.

Adaptation to Social-Ecological Change in Northwestern Pakistan: Household Strategies and Decision-making Processes.

Values are important factors shaping people's perceptions of social-ecological changes and the associated impacts, acceptable risk, and successful adaptation to various changes; however, little empirical work has examined how values interact to influence adaptation decision-making. We drew on 25 semi-structured interviews with community leaders, farmers, fisherfolk, and individuals in the tourism industry in northwestern Pakistan to identify types of adaptations employed by households and explore what values were present in these households' adaptation decisions. Our results show that households frequently employed environmental management and livelihood diversification to adapt to a wide range of social-ecological change. We found that multiple values influenced household adaptation and that employing an adaptation strategy often involved a tradeoff of values. We also found that household adaptations were embedded in multi-scalar social, cultural, economic, and political processes that could constrain or conflict with such adaptations. Overall, our research illustrates the complex influence of values on household adaptation decisions and highlights the need to further understand how adaptations are aligned, or misaligned, with stakeholders' diverse values in order to inform more equitable adaptation to social-ecological change.

Psychometric analysis of cognitive distortions scale-urdu on patients diagnosed with mental disorders.

OBJECTIVE: To assess the reliability and concurrent validity of Cognitive Distortions Scale-Urdu based on Beck's Cognitive Model of psychopathology on patients diagnosed with mental disorders. METHODS: The correlational study was conducted from June 15, 2019, to January 30, 2020, in Lahore, Pakistan, and comprised psychiatric patients of either gender aged 18-65 years from six government hospitals, including Mayo Hospital, Services Hospital, Punjab Institute of Mental Health, Sir Ganga Ram Hospital, Gulab Devi Hospital and the Combined Military Hospital. The participants completed the demographic information form and the Cognitive Distortions Scale-Urdu. The latter was re-administered after a gap of two weeks to determine its internal consistency and test-retest reliability. Feinstein Paranoia, Subjective Wellbeing and Siddiqui Shah Depression Scales were administered along with the Cognitive Distortions Scale-Urdu to determine its concurrent validity. Statistical analysis was done using SPSS 24. RESULTS: Of the 106 patients, 56(52.8%) were recruited for reliability analysis with an overall mean age of 32.31±10.62 years, and 50(47.2%) for concurrent validity analysis with an overall mean age of 31.30±10.52 years. Correlation analysis indicated good internal consistency (α=0.87), test retest reliability (r=0.86) and moderately high concurrent validity of the scale (range: 0.44-0.89). CONCLUSIONS: The Cognitive Distortions Scale-Urdu was found to have sound psychometric properties and was suitable for researchers to obtain quantitative estimates of the frequency and intensity of cognitive distortions in clinical samples.

Identification of a novel biallelic missense variant in the KIAA0825 underlies postaxial polydactyly type A.

Postaxial polydactyly (PAP) is characterized by development of extra digits, which mostly segregates in autosomal recessive pattern. The underlying genetic cause of recessive non-syndromic PAP type A has been associated with sequence variants in five different genes (ZNF141, IQCE, GLI1, FAM92A, KIAA0825). The present study was aimed to investigate clinical and genetic causes of PAPA in a consanguineous family of Pakistani origin. Microsatellite-based linkage analysis was used to search for the disease-causing gene. Linkage in the family was established at chromosome 5q15 harbouring a candidate gene KIAA0825. Subsequently, Sanger sequencing revealed a novel homozygous missense variant [c.50T>C; p. (Leu17Ser)] in the gene, which co-segregated with the disease within the family. Protein structural analysis predicted a substantial change in the secondary structure of the mutant protein affecting its function. This is the third disease causing variant identified in the KIAA0825. This has not only expanded spectrum of the mutations in the gene but also further substantiated its role in the limb development in human.

Faecal and nitrate contamination in the groundwater of Mardan district, Pakistan.

This study aimed to determine the status of groundwater contamination with faecal coliform and nitrate in the rural areas of Mardan district, Pakistan. Both analytes require regular monitoring according to the National Environmental Quality Standards (NEQS) of Pakistan. Groundwater samples (n = 100) were collected from 25 villages across four zones. Samples were analysed for physicochemical parameters including pH, electrical conductivity (EC), Escherichia coli (E. coli) contamination, nitrite, and nitrate ([Formula: see text] and [Formula: see text]). Whilst the average concentrations of [Formula: see text] in the water samples were within the permissible limits of 50 mg L-1 set by the World Health Organisation (WHO) and NEQS two villages exceeded the safety limits. Non-carcinogenic health risks of [Formula: see text] were estimated in terms of average daily dose (ADD) and hazard quotient (HQ). The HQ values for [Formula: see text] were > 1 for children signifying potential health risks; however, the adult population had HQ < 1 which indicates no risk. Groundwater samples tested positive for E. coli contamination in 13 villages, suggesting that residents may be living at risk of various microbial diseases due to drinking of contaminated water. The findings of this study provide valuable baseline data for groundwater researchers, policymakers, and the local public health department.

Mechanisms of change and participant outcomes in a Recovery Education Centre for individuals transitioning from homelessness: a qualitative evaluation.

BACKGROUND: Recovery Education Centres (RECs) are increasingly implemented to support the process of recovery for individuals experiencing mental health challenges. However, the evidence on key REC mechanisms and outcomes, particularly for diverse subpopulations or service delivery contexts is scant. This study identified mechanisms and outcomes of an REC focused on adults with mental health challenges transitioning from homelessness. METHODS: Qualitative methods were used to explore in-depth the experiences of homeless and unstably housed participants experiencing mental health challenges in Toronto, Canada. Twenty service users participated in semi-structured interviews between July 2017 and June 2018, six to 14 months following REC enrollment. A realist informed interview guide explored participants' perspectives on key REC mechanisms and outcomes. Interviews were audio-recorded, transcribed verbatim and analyzed using inductive thematic analysis. Investigator triangulation and member checking processes enhanced analytical rigour. RESULTS: Participants perceived that program participation supported the process of recovery through several mechanisms: a judgment-free environment; supportive relationships, mutuality and role modelling; deconstruction of self-stigma; and reclaiming of one's power. Participants described several outcomes at the personal, interpersonal and social levels, including improvements in health and well-being; self-esteem, confidence and identity; sense of empowerment, control and personal responsibility; as well as improvements in interpersonal skills, pro-social behaviours and ability to self-advocate; and increased goal development and future orientation. CONCLUSIONS: Findings suggest RECs can support the process of recovery among people transitioning from homelessness and can successfully support subpopulations experiencing mental health challenges and social disadvantage.

Association of sequence variants in frizzled-6 with autosomal recessive nail dysplasia (NDNC-10) in Pashtun families.

Primitive epidermis develops the nail apparatus. Nails have a strong and inflexible nail plate at the end of each digit. Very few genes responsible for causing nonsyndromic form of nail dysplasia have been reported. In the current study, peripheral blood samples were collectedfrom three unaffected individuals and four affectedindividuals of Family A, while blood from two affected and three unaffected individuals were taken of Family B. Genotyping in both the families was performed using highly polymorphic short tandem repeat microsatellite markers. Sanger sequence of the FZD6 gene was performed and analysed for segregation analysis. A comparative modelling approach was used to predict the three-dimensional structures of FZD-6 protein using Modeller 4. Linkage analysis mapped a disease locus on chromosome 8q22.3, harbouring FZD6. Targeted Sanger sequencing of all the coding exons of FZD6 revealed a nonsense sequence variant in pedigree A, whereas a missense sequence variant in pedigree B. Finding and literature indicates the disease spectrum of Pakistani population with claw-shaped nail dysplasia, particularly in families of Pashtun origin.

Association between obesity and risk of knee osteoarthritis.

The study was designed to investigate the association between obesity and the risk of knee osteoarthritis, recruiting 400 knee osteoarthritis patients and an equal number of controls. After the informed consent, diagnosed patients from Jinnah Post Graduate Medical Centre, Karachi were included as "cases". Age-matched individuals without the disease were included as "controls". Sociodemographic data were taken from each participant. Characteristics were compared by odds ratio and chi-square using SPSS 20 software. Obesity (OR 3.29; 95% CI 2.40-4.51), female gender (OR 2.87; 95% CI 1.94-4.25) and family history (OR 3.61; 95% CI 2.69-4.85) were found to be significantly associated with osteoarthritis (p<0.001). Highest OR was found in case of stair climbing >10 flights/d (OR 6.08; 95% CI 4.16-8.89; p<0.001), whereas heavy lifting (>25 kg/d for > 4 hr) was observed as another major factor with OR of 5.24 (95% CI 3.54-7.75; p<0.001) that elevates the risk. The study concluded that obesity is significantly associated with osteoarthritis and obese individuals (BMI>25 kg/m2) are at high risk of disease development. Furthermore, family history, prolonged standing (>2 h/d for >1 yr), heavy lifting (>25 kg/d for > 4 hr), stair climbing (>10 flights/d) and sitting on the floor (>5 h/d) might also be associated with knee osteoarthritis.

Effect of paroxetine on intestinal motility in the presence of ondansetron.

Chemotherapy, radiotherapy, surgery and depression are the conditions that run in parallel fashions. All these conditions cause the release of an increased amount of serotonin in the body. Serotonin acts on these 5HT3 receptors and causes nausea and vomiting. Ondansetron acts by blocking serotonin from acting on the receptors and thus is useful in decreasing episodes of nausea and vomiting but when used concomitantly with SSRIs (selective serotonin reuptake inhibitors) as cancer patient also suffered from depression. This combination tends to decrease the efficacy of ondansetron. The present study was carried out to observe the modulatory role of ondansetron on ileal smooth muscle motility in vitro. Experiments were performed in four groups (n=6) and ileal smooth muscle activity was recorded on the power lab (USA). The effects of increasing concentrations of serotonin, ondansetron and paroxetine alone were observed. In the fourth group effects of paroxetine in the presence of fixed concentration (1ml) of ondansetron (10-6M) was observed. The maximum response obtained by serotonin served as a control for our study (100%). Paroxetine response on intestinal motility was completely blocked in the presence of ondansetron. Our findings hence, reinforce the hypothesis that paroxetine decreases the antiemetic activity of serotonin antagonist ondansetron, by super sensitization of serotonergic receptors resulting in an increased incidence of nausea and vomiting in cancer patient despite adequate antiemetic prophylaxis.

Dioxin leaching risk assessment through selected soils by estimating distribution coefficient and breakthrough curves.

From health and environmental point of views, dioxins are important due to their toxicity and persistence. Dioxins have the potential to reside in the environment for longer time if sorbed onto the clay and organic content of the soil matrix. Their transport or leaching under certain environmental conditions such as preferential flow can increase the risk of groundwater contamination. In the current study, breakthrough curves (BTCs) against time were plotted for selected dioxin transport prediction; based on measured distribution coefficient (Kd), dispersion coefficient (D), and retardation factor (R). Three representative soil series named Burhan, Warsak, and Kunda were selected. For dibenzo-p-dioxin (DD), Kd values followed the order as: Burhan> Warsak > Kunda, while for 2-chloro dibenzo-p-dioxin (2 Cl-DD), Kd values followed an order as: Kunda > Burhan > Warsak. Dioxin transport was measured at two different linear velocities (20 and 50 cm day-1). Attainment of equilibrium was verified to be dependent upon the Kd, R, D, and chlorination on dioxin. Kunda series with low OM (0.6%), clay (0.2%), and R (377) was found to have relatively high DD transport potential under normal velocity, due to high dispersion values for its sandy nature. Under the steady or preferential flow conditions, all the plots obtained were identical irrespective of soil type and dioxin nature.

Case Of Xanthogranulomatous Oophoritis.

Xanthogranulomatous inflammation is characterized by destruction of the tissues of the organ involved and replacement by chronic inflammatory cells such as lymphocytes, plasma cells, occasional neutrophils with or without multinucleated or Touton giant cells. Exact aetiology is not known but the theory of infection with organisms like Proteus, E coli, and Bacteroides fragilis is most popular. Xanthogranulomatous inflammation of the female genital tract is not common and usually involves the endometrium; however, xanthogranulomatous inflammation of the ovaries is a rare entity.

Paroxetine: An update of response on intestinal motility.

OBJECTIVE: To find out the possible effects of paroxetine on gastrointestinal smooth muscles in vitro as they can cause severe nausea and vomiting at the start of therapy which later settles down. METHODS: Power lab (USA) was used for recording the contractions of ileal smooth muscle of rabbits in response to acetylcholine, serotonin and paroxetine. RESULTS: The percent responses with acetylcholine, serotonin and paroxetine were 100, 158.7 and 6.45 percent respectively indicating that acetylcholine and serotonin causes an increase in contractility of isolated ileal smooth muscle in comparison to paroxetine which has a depressant effect on motility. CONCLUSIONS: Inability of paroxetine to enhance the serotonergic transmission in vitro causes a decrease in its qualitative response.

Histological Pattern Of Endometrial Samples In Postmenopausal Women With Abnormal Uterine Bleeding.

BACKGROUND: Abnormal uterine bleeding is one of the most common clinical problems in gynaecological practice and is an indicator of various underlying disorders. An endometrial biopsy should be done in all women over 35 years with AUB to rule out endometrial cancer or pre-malignant lesion and to initiate treatment. However, wide range of histological patterns on endometrial biopsy offer a diagnostic challenge to practicing pathologists. The objective of this study was to determine histological patterns of endometrium in postmenopausal women with abnormal uterine bleeding. METHODS: This cross-sectional study was conducted in the department of obstetrics and gynaecology, Benazir Bhutto Shaheed women and children teaching hospital, Abbottabad from 15/11/2014 to 14/05/2015. This study involved 110 postmenopausal women presenting with abnormal uterine bleeding. A written informed consent was obtained from every patient. RESULTS: The mean age of the patients was 61.60±6.17 years and the mean duration of AUB was 5.20±2.80 years. Most of the patients were para 6 (28.2%) and para 5 (28.2%) followed by para 4 (18.2%) and para 3 (17.3%) while only 8.2% were para 1. The most common histological pattern observed was complex hyperplasia without atypia (30.9%) followed by atrophic endometrium (24.5%), simple hyperplasia (23.6%), malignancy (12.7%), complex hyperplasia with atypia (4.5%) and benign endometrial polyp (3.6%). When stratified the data, there was no significant difference of histological patterns across various age groups (p=.673), duration of AUB (p=.064) and parity (p=.242). CONCLUSIONS: The most common histological pattern observed in postmenopausal women with AUB was complex hyperplasia without atypia (30.9%) followed by atrophic endometrium (24.5%), simple hyperplasia (23.6%), malignancy (12.7%), complex hyperplasia with atypia (4.5%) and benign endometrial polyp (3.6%).

Out Come Of Trial Of Scar In Patients With Previous Caesarean Section.

BACKGROUND: Patients who had one caesarean section were previously not given a trial of scar due to fear of increased morbidity. However, recently there has been a trend to give a trial of labour to patients with a previous caesarean section for a non-recurrent cause. Medical evidence indicates that 60-80% of women can achieve vaginal delivery after a previous lower segment caesarean section. Proper selection of patients for trial of scar and vigilant monitoring during labour will achieve successful maternal and perinatal outcome. The objective of our study is to establish the fact that vaginal delivery after one caesarean section has a high success rate in patients with previous one caesarean section for non-recurrent cause. METHODS: The study was conducted in Ayub Teaching Abbottabad, Gynae-B Unit. All labouring patients, during the study period of five years, with previous one caesarean section and between 37 weeks to 41 weeks of gestation for a non-recurrent cause were included in the study. Data was recorded on special pro forma designed for the purpose. Patients who had previous classical caesarean section, more than one caesarean section, and previous caesarean section with severe wound infection, transverse lie and placenta previa in present pregnancy were excluded. Foetal macrosomia (wt>4 kg) and severe IUGR with compromised blood flow on Doppler in present pregnancy were also not considered suitable for the study. Patients who had any absolute contraindication for vaginal delivery were also excluded. RESULTS: There were 12505 deliveries during the study period. Total vaginal deliveries were 8790 and total caesarean sections were 3715. Caesarean section rate was 29.7%. Out of these 8790 patients, 764 patients were given a trial of scar and 535 patients delivered successfully vaginally (70%). Women who presented with spontaneous onset of labour were more likely to deliver vaginally (74.8%) as compared to induction group (27.1%). CONCLUSIONS: Trial of vaginal birth after caesarean (VBAC) in selected cases has great importance in the present era of the rising rate of primary caesarean section.

Decompressive Craniectomy For Acute Subdural Haematoma With Expansile Duraplasty Versus Dural-Slits.

BACKGROUND: Traumatic subdural hematoma is one of the lethal injuries to brain. Various surgical techniques are used to evacuate the acute subdural hematoma. The hematoma evacuation can either be done by opening of dura by multiple slits or by opening of dura in single large c shape and then doing the expansile duraplasty. Present study aimed to compare both these techniques. METHODS: This randomized control study was conducted in department of neurosurgery, Ayub Medical College, Abbottabad from July 2011 to July 2013. A total of 59 patients were included in this study, which were randomly allocated in two groups (i.e., group A and group B) for decompressive craniectomy. Thirty-one patients were operated by craniectomy with full dural flap opening (Group A), and 28 patients were operated by craniectomy with multidural-slits (Group B). Glasgow Outcome score (GOS) at 6 weeks after the surgery was used to determine the outcome. RESULTS: Mean age of the patients was 33.4±12.8 years. Majority were males. In group A 51.6 % (16) of the patients survived out of which a favourable outcome (GOC 3-5) was observed in 41.9% of the patients, and 9.1% of patients ended up in vegetative state. While in group B 46.4% (13) of the patients survived among which favourable outcome was seen in 39.3% of patients and 7.1% of patients ended up in vegetative state. The difference in outcome measure is insignificant. CONCLUSIONS: There was no statistically significant difference among the two groups as regards the mortality, GOS, frequency of complications and hospital. While the duration of surgery was significantly shorter in patients operated with dural slits.

Ondansetron: A newer aspect of dose response relationship on ileal smooth muscles of rabbit.

There are several life threatening deadly diseases in our world but 'Cancer' out powers them all in recent years. Chemotherapy may be used on its own or an adjunct to other forms of therapy. Despite the advancement in cytotoxic drug therapy and supportive treatment almost 70% of patient suffer from chemotherapy induced nausea and vomiting (CINV). Ondansetron, a 5-HT(3) receptor antagonist has now become a gold standard in the treatment of chemotherapy induced nausea and vomiting. The central actions of ondansetron are well established but its peripheral actions are not well recognized. The aim of our study was to explore the peripheral actions of ondansetron. Experiments were performed in five groups (n=6) and ileal smooth muscles activity was recorded on power lab (USA). The effects of increasing concentrations of acetylcholine, serotonin & ondansetron alone was observed in first three groups. In the next two groups effects of acetylcholine and serotonin pretreated with fixed concentration (1ml) of ondansetron (10¯Ï– M)were studied. The maximum response obtained by acetylcholine served as a control for our study. Maximum response with acetylcholine was taken as 100% and with serotonin was 177 percent of control. Cumulative dose response curve with ondansetron was triphasic. At 10¯ψM it was 28.8%, whereas with 10¯ξM the amplitude decreased to 16.87%, it reached to plateau at 10¯Ï– M. Response of acetylcholine & serotonin was decreased to 57% and 78% respectively in the presence of fixed concentration of ondansetron (10¯Ï– M). Ondansetron reduces the acetylcholine and serotonin induced gastrointestinal motility. Our study has indicated that ondansetron apart from having central action also has marked peripheral actions that play an important role in CINV and may act as a partial agonist.

A comparative study of the beneficial effects of ipratropium and beclomethasone against insulin-induced tracheal tissue contraction in a guinea pig model.

OBJECTIVE: To evaluate the acute effects of insulin on airway reactivity and the protective effects of beclomethasone and ipratropium against insulin-induced airway hyperresponsiveness on isolated tracheal smooth muscle in a guinea pig model. MATERIALS AND METHODS: The trachea of each guinea pig was excised; one end of the tracheal strip was attached to the hook of the oxygen tube of a tissue bath and the other end was connected to a research-grade isometric force displacement transducer. The effects of varying concentrations of insulin (10(-7) to 10(-3)M) and insulin pretreated with a fixed concentration of beclomethasone (10(-6)M) and ipratropium (10(-6)M) on the isolated tracheal tissue were studied by constructing cumulative concentration-response curves. Changes in tracheal smooth muscle contractions were recorded on a 4-channel oscillograph. RESULTS: The means ± standard error of the mean of the maximum amplitude of contraction with increasing concentrations of insulin and of insulin pretreated with fixed concentrations of beclomethasone and ipratropium were 35 ± 1.13, 22 ± 1.15 and 27.8 ± 1.27 mm, respectively. CONCLUSION: The data showed that beclomethasone inhibited the contractile response of insulin to a greater extent than ipratropium. Thus we suggest that inhalational insulin pretreated with beclomethasone may be more efficacious than with ipratropium for the amelioration of potential respiratory adverse effects such as bronchoconstriction.