Clinical Profile of Chronic Kidney Disease Patients in Rural Population of Haryana: A Single-center Experience

Background: CKD is a major health problem associated with high morbidity and mortality. Chronic kidney disease is end result of long standing cases of diabetes mellitus and hypertension. There is paucity of data, regarding spectrum of CKD. CKD is generally asymptomatic in early stages. Early interventions delay the progression to ESRD, thus reducing morbidity and mortality. Objectives: To study the Clinical profile, Biochemical profile and determine the Aetiology of chronic kidney disease among Rural population. Methods: In this study, we retrospectively analysed data of 161 patients admitted in hospital over a period of six months. Data was collected based on clinical assessment, laboratory analysis and Radiological investigations to determine aetiology of chronic kidney disease. Results: 161 patients of chronic kidney disease were included in the study. The mean age of all patients studied was 47.20±16.16 years. The most common aetiology was hypertensive nephropathy. Most of the patients presented with, pedal oedema (59.6%) followed by Oliguria (52.2%), facial edema (46.9%). Conclusion: The major causes of CKD in descending order were hypertension, Type 2 diabetes mellitus, chronic glomerulonephritis and obstructive uropathy. So if we are able to detect and treat these conditions in early phase, we can prevent further progression and damage to the kidney.

A questionnaire-based comparison of conventional teaching methods to computer assisted learning in experimental pharmacology for undergraduate medical students

Background: Computer Assisted Learning (CAL) for teaching experimental pharmacology is now widely accepted as alternative to animal experiments. The objective of this study was to compare the performance of undergraduate medical students by conventional teaching methods (lecture and discussion) and CAL.Methods: This was a questionnaire based observational study involving 109 MBBS students of fifth semester. The students were taught experimental pharmacology practical by both conventional methods (lecture with discussion) and computer assisted learning (CAL). Questionnaire and their filled responses by these students were taken at the end of lecture-discussion (pre-CAL) and after the CAL experiments (post-CAL), covering the same topics of experimental pharmacology. Pre-CAL and post-CAL data were assessed statistically.Results: In the pre-CAL session, only 53.39%, 47.56%, 53.39% and 49.5% of the students were having the scores above 40% in the rabbit eye, DRC and potentiation, frog heart and dog BP experiment respectively, which was increased to 77.44%, 75.48%, 75.47% and 75.48% of the students respectively in the post-CAL assessment. A statistically significant difference (p <0.05) in the performance was observed among the students in the pre-CAL and post-CAL assessment.Conclusions: CAL is a good alternative to animal experimentation. Lecture with discussion, followed by CAL experiments on the same topics, enhanced the performance of students as shown by improvement in post-CAL scores.

Iodine Deficiency Disorder in Children Aged 6-12 Years of Ambala, Haryana.

We conducted this study to assess the prevalence of goitre among 2700 children (6-12 yr) of district Ambala in Haryana. Children were examined as per standards laid by National iodine deficiency disorder control programme (NIDDCP). Multi stage cluster sampling method was used. Urine and salt samples were also studied for iodine concentration. The overall prevalence of goitre in the studied subjects was 12.6%. The median urinary iodine excretion in the study sample was more than 100μg/L Iodine content was found to be adequate in 88% of salt samples. We conclude that there was a high prevalence of goitre in young children despite iodine repletion. This calls for identification of factors to strengthen NIDDCP and the need to emphasize use of iodized salt in Haryana.

Prescribing pattern of drugs in the outpatient department of a tertiary care teaching hospital in Ghaziabad, Uttar Pradesh.

The study was done to find out the current prescribing pattern in this tertiary care teaching hospital in Ghaziabad. The study was carried out at Santosh Medical College and Hospital over a period of 3 months. A total of 500 prescriptions were collected and analyzed. Total number of drugs prescribed was 1450 out of which 564 drugs were prescribed by generic names. Average number of drugs was 2.9. 327 drugs were fixed dose combinations while only 595 were from essential drug list. The mean number of drugs per prescription should be as low as possible otherwise there is increase risk of drug interaction, bacterial resistance, non-compliance and increase in cost The prescribing practices are more of irrational types like polypharmacy, use of vitamins and injections, less number of drugs by generic names and lesser drugs from Essential Drug List. There is an urgent need for some interventions to improve the situation.

Prevalence and pattern of substance abuse among school childern in nothern India: A rapid assesment study.

Background: Substance abuse among children has become an issue of concern throughout the world. Increasing substance abuse and its impact on physical and psychosocial health is a worldwide public health concern affecting the early youth and subsequently the whole life of the individuals. Particularly disturbing fact is that the age of initiation of abuse is progressively falling. To plan effective interventions, it is essential to have information on the extent and type of substance abuse among school children and their attitude towards its control. Aims & Objective: To find out the prevalence and pattern of substance abuse among school children and the associated risk factors. Material and Methods: A descriptive cross-sectional survey was conducted among students (13-19 years) studying in classes 7th-12th in rural and urban areas of district Ambala, using the Self-Administered WHO Model Core Questionnaire. Stratified random sampling technique was used to select the respondents. A total of 1500 students studying in various government and private schools were taken for the study purpose. Results: Overall prevalence of substance abuse was 60.0% for ever users and 34.93% for regular users. Substance abuse was more among male urban students belonging to nuclear families (p<0.001). Among ever users, alcohol (44.49%) was the most common substance abused while tobacco (14.42%) was mostly consumed by regular users. Substance abuse was more in age group of 17-19 years. Overall 42% were using more than one drug combination. Conclusion: Prevalence of substance use among school children in Northern India is high and causes significant physical and psychosocial problems in this population. A large proportion of those using drugs reported serious adverse effects, raising the necessity of targeted interventions to reduce the risk of subsequent substance dependence and other deleterious consequences.

Healing effects of Aegle marmelos (L.) Correa fruit extract on experimental colitis.

Graded doses of 50% ethanolic extract of dried fruit pulp of Aegle marmelos (AME) (100, 200 and 400 mg/kg) daily for 14 days in acetic acid (AA)-induced colitis in rats showed 200 mg/kg of AME as an optimal effective dose against AA-induced colonic damage score and weight. This dose (200 mg/kg; po) was further studied in AA-induced colitis for its effects on various physical (mucous/blood in stool, food and water intake and body weight changes), histology, antibacterial activity and biochemical parameters like free radicals (nitric oxide and lipid peroxidation), antioxidants (superoxide dismutase, catalase and reduced glutathione) and myeloperoxidase (acute-inflammatory marker) activities in rat colonic tissue. AME decreased colonic mucosal damage and inflammation (macroscopic and microscopic), mucous/bloody diarrhea, fecal frequency and increased body weight affected in AA-induced colitis. AME showed significant antibacterial activity and enhanced the antioxidants but decreased free radicals and myeloperoxidase activities thereby decreasing tissue damage and inflammation and thus, affording ulcer healing. The above effects of A. marmelos authenticated its use in indigenous system of Medicine.

Immunomodulatory effect of Moringa oleifera Lam. extract on cyclophosphamide induced toxicity in mice.

Immunomodulatory effect of ethanolic extract (50%) of M. oleifera leaves (MOE) has been studied in normal and immunosuppressed mice models. Different doses of MOE i.e. 125, 250 and 500 mg/kg body weight of mice were administered orally for 15 days. Cyclophosphamide at a dose of 30 mg / kg body weight was administered orally for the next 3 days. On day 16 and 19, hematological parameters like white blood cell (WBC) count, red blood cell (RBC) count, haemoglobin level (Hb), percent neutrophils and organ weight were recorded. Effect of MOE on phagocytic activity of mice macrophages was determined by carbon clearance test. MOE showed significant dose dependent increase in WBC, percent neutrophils, weight of thymus and spleen along with phagocytic index in normal and immunosuppressed mice. The results indicate that MOE significantly reduced cyclophosphamide induced immunosuppression by stimulating both cellular and humoral immunity.

Antidiabetic and antiulcer effects of extract of eugenia jambolana seed in mild diabetic Rats : Study on gastric mucosal offensive acid-pepsin secretion.

Diabetes has been reported to increase propensity to peptic ulceration through its effect both on offensive and defensive mucosal factors. Seeds of Eugenia jambolana (EJ) have been reported to have both antidiabetic as well as ulcer protective effects. The present study evaluates the antidiabetic effects of ethanolic extract of dried seed kernel of Eugenia jambolana (EJE) and its comparative effect on gastric ulceration and acidpepsin secretion with standard antisecretory FL-blocker. Ranitidine and antidiabetic glibenclamide with a premise that Eugenia jambolana may show better ulcer healing effects by promoting defensive or reducing offensive mucosal factors in mild diabetes (MD) rats. MD was produced in adult rats by administration of streptozotocin (45 mg/kg, ip). EJE was given orally in the doses of 100–400 mg/kg for 10 days and in the dose of 200 mg/kg for 30 days respectively to study its dose- and time-dependent effects on various diabetic parameters like blood glucose, serum cholesterol and triglycerides, insulin level and glycosylated hemoglobin. For ulcer protective and gastric secretion studies, EJE (200 mg/kg) was given orally for 10 days against 2 h cold restraint stress (CRS)-, 4 h pylorus ligation (PL), aspirin (ASP, 200 mg/kg, 4 h) – and 95% ethanol (EtOH, 1 ml/200 g, 1 h)-induced gastric ulcers and offensive acid-pepsin secretion after 4 h PL with cooccurring MD in rats. EJE showed dose-dependent decrease in blood glucose level in MD rats. Blood glucose level remained stable in mild diabetic rats from 3rd day onwards after streptozotocin administration (taken as 1st day for treatment) and EJE (200 mg/kg) showed anti-hyperglycemic effect on 10th day of its administration. Further, EJE in the above dose also decreased cholesterol level with little or no effect on triglycerides level and reversed the decrease and increase in insulin and glycosylated hemoglobin level near to the normal level as observed alter 30 days treatment in MD rats. MD rats exhibited an increased propensity to gastric ulceration induced by CRS, ASP, EtOH and PL and caused increase in acid-pepsin secretion. EJE was not only effective in reversing the increased propensity to ulceration in diabetic rats but also decreased the acid-pepsin output better than glibenclamide. The ulcer protective effect of Eugenia Jambolana seems to be due to its antidiabetic and gastric antisecretory effects.

Ulcer healing properties of ethanolic extract of eugenia jambolana seed in diabetic rats : Study on gastric mucosal defensive factors.

Diabetes has been reported to cause an increase in offensive and decrease in defensive gastric mucosal factors, the imbalance of which can cause ulceration and delay the ulcer healing. Eugenia jambolana has been documented to have both antidiabetic and antiulcer activities. The present study evaluates the effects of ethanolic extract of E. jambolana on gastric ulcer healing and on rat gastric mucosal defensive factors in gastric ulcer with co-occurring diabetes. E. jambolana extract was administered orally in the dose of 200 mg/kg once daily for 10 days. E. jambolana extract increased mucin secretion, mucosal glycoprotein and glutathione levels and decreased the lipid peroxidation in gastric mucosa of diabetic rats. Its treatment also reversed the decrease in life span of gastric mucosal cells as indicated by decreased cell shedding in the gastric juice but found to have no effect on cell proliferation, indicating enhanced defensive status. E. jambolana extract was effective in reversing the delayed healing of gastric ulcer in diabetic rats near to the normal level. E. jambolana showed better ulcer healing effect than glibenclamide, because of its both antihyperglycemic and mucosal defensive actions. It could thus, be a better choice for treating gastric ulcers co-occurring with diabetes.

Evaluation of wound healing activity of extracts of plantain banana (Musa sapientum var. paradisiaca) in rats.

Plantain banana (M. sapientum var. paradisiaca, MS) has been shown to possess ulcer healing activity. The present work with plantain banana was undertaken with the premise that the drug promoting ulcer healing could have effect on wound healing also. Wound healing activity of MS was studied in terms of (i) percent wound contraction, epithelization period and scar area; (ii) wound breaking strength and (iii) on granulation tissue antioxidant status [estimation of superoxide dismutase (SOD) and reduced glutathione (GSH), free radical (lipid peroxidation, an indicator of tissue damage) and connective tissue formation and maturation (hexuronic acid, hydroxyproline and hexosamine levels)] in excision, incision and dead space wound models respectively. The rats were given graded doses (50-200 mg/kg/day) of aqueous (MSW) and methanolic (MSE) extracts of MS orally for a period of 10-21 days depending upon the type of study. Both extracts (100 mg/kg) when studied for incision and dead space wounds parameters, increased wound breaking strength and levels of hydroxyproline, hexuronic acid, hexosamine, superoxide dismutase, reduced glutathione in the granulation tissue and decreased percentage of wound area, scar area and lipid peroxidation when compared with the control group. Both the extracts showed good safety profile. Plantain banana thus, favoured wound healing which could be due to its antioxidant effect and on various wound healing biochemical parameters.

Effect of ethanolic extract of root of Pongamia pinnata (L) pierre on oxidative stress, behavioral and histopathological alterations induced by cerebral ischemia--reperfusion and long-term hypoperfusion in rats.

Possible effect of an ethanolic root extract of Pongamia pinnata (L) Pierre (P. pinnata) on oxidant-antioxidant status and histopathological changes in acute ischemia-reperfusion injury in the rat forebrain have been investigated. Further, its effect was also assessed on long-term cerebral hypoperfusion-induced changes in anxiety, cognitive and histopathological parameters. Cerebral post-ischemic reperfusion is known to be associated with generation of free radicals. In the present study, bilateral common carotid artery occlusion (BCCAO) for 30 min followed by 45 min reperfusion produced increases in lipid peroxidation, superoxide dismutase (SOD) activity and a fall in the total tissue sulfhydryl (T-SH) levels. The ethanolic extract of roots of P. pinnata (50 mg kg(-1), po for 5 days) attenuated the ischemia-reperfusion-induced increase in lipid peroxidation, SOD activity and a fall in T-SH levels. The extract also ameliorated histopathological changes and inflammatory cell infiltration in the frontoparietal region of the rat brain. The extract (50 mg kg(-1), po for 15 days) was also found to alleviate the long-term hypoperfusion-induced anxiety and listlessness (open field paradigm). There was an improvement of learning and memory deficits (Morris' water maze testing). It also attenuated reactive changes in forebrain histology like gliosis, lymphocytic infiltration, astrocytosis and cellular edema. Results suggest protective role of P. pinnata in ischemia-reperfusion injury and cerebrovascular insufficiency states.

Effect of ethanolic extract of Eugenia jambolana seeds on gastric ulceration and secretion in rats.

Eugenia jambolana (Jamun) fruit has been reported to give soothing effect on human digestive system. Present study includes the effect of ethanolic extract of seeds of E. jambolana (EJE) against gastric ulcers induced by 2 h cold restraint stress (CRS), aspirin (ASP, 200 mg/kg, 4 h), 95% ethanol (EtOH, 1 ml/200 g, 1 h) and 4 h pylorus ligation (PL) in rats. To ascertain the mechanism of action of EJE, its effect was studied on mucosal offensive acid-pepsin secretion, lipid peroxidation (LPO, free radical) and defensive mucin secretion, cell proliferation, glycoprotein and glutathione (GSH, an antioxidant). Acute and subacute toxicity studies were also conducted for the safety profile of Eugenia jambolana. EJE 200 mg/kg, when administered orally for 10 days in rats was found to reduce the ulcer index in all gastric ulcer models. It tended to decrease acid-pepsin secretion, enhanced mucin and mucosal glycoprotein and decreased cell shedding but had no effect on cell proliferation. It showed antioxidant properties indicated by decrease in LPO and increase in GSH levels in the gastric mucosa of rats. Acute toxicity study indicated LD50 to be more than 10 times (>2000 mg/kg) of the effective ulcer protective dose while subactue toxicity study (>1000 mg/kg) indicated no significant change in the general physiological and haematological parameters, liver and renal function tests. The result of the present study indicates that E. jambolana seed has gastro-protective properties mainly through promotion of mucosal defensive factors and antioxidant status and decreasing lipid peroxidation.

Teratogenicity of Asparagus racemosus Willd. root, a herbal medicine.

Asparagus racemosus (AR) is a herb used as a rasayana in Ayurveda and is considered both general and female reproductive tonic. Methanolic extract of A. racemosus roots (ARM; 100 mg/kg/day for 60 days) showed teratological disorders in terms of increased resorption of fetuses, gross malformations e.g. swelling in legs and intrauterine growth retardation with a small placental size in Charles Foster rats. Pups born to mother exposed to ARM for full duration of gestation showed evidence of higher rate of resorption and therefore smaller litter size. The live pup showed significant decrease in body weight and length and delay of various developmental parameters when compared to respective control groups. AR therefore, should be used in pregnancy cautiously as its exposure during that period may cause damage to the offspring.

Effect of aqueous extract of neem (Azadirachta indica) leaves on offensive and diffensive gastric mucosal factors in rats.

Standardized aqueous extract of Neem (Azadirachta indica) leaves (AIE) has been reported to show both ulcer protective and ulcer healing effects in normal as well as in diabetic rats. To study the mechanism of its ulcer protective/healing actions, effects of AIE (500 mg/ kg) was studied on various parameters of offensive acid-pepsin secretion in 4 hr pylorus ligation, pentagastrin (PENTA, 5 microg/kg/hr)-stimulated acid secretion and gastric mucosal proton pump activity and defensive mucin secretion including life span of gastric mucosal cells in rats. AIE was found to inhibit acid-pepsin secretion in 4 hr pylorus ligated rats. Continuous infusion of PENTA significantly increased the acid secretion after 30 to 180 min or in the total 3 hr acid secretion in rat stomach perfusate while, AIE pretreatment significantly decreased them. AIE inhibited the rat gastric mucosal proton pump activity and the effect was comparable with that of omeprazole (OMZ). Further, AIE did not show any effect on mucin secretion though it enhanced life span of mucosal cells as evidenced by a decrease in cell shedding in the gastric juice. Thus, our present data suggest that the ulcer protective activity of AIE may be due to its anti-secretary and proton pump inhibitory activity rather than on defensive mucin secretion. Further, acute as well as sub acute toxicity studies have indicated no mortality with 2.5 g/kg dose of AIE in mice and no significant alterations in body or tissues weight, food and water intake, haematological profile and various liver and kidney function tests in rats when treated for 28 days with 1 g/kg dose of AIE.

Effect of plantain banana on gastric ulceration in NIDDM rats: role of gastric mucosal glycoproteins, cell proliferation, antioxidants and free radicals.

Methanolic extract of Musa sapientum var. Paradisiaca (MSE, 100 mg/kg) was studied for its antiulcer and mucosal defensive factors in normal and non-insulin dependent diabetes mellitus (NIDDM) rats. NIDDM was induced by administering streptozotocin (STZ, 70 mg/kg, ip) to 5 days old rat pups. The animals showing blood glucose level >140mg/dL after 12 weeks of STZ administration were considered as NIDDM positive. Effects of MSE were compared with known ulcer protective drug, sucralfate (SFT, 500 mg/kg) and anti-diabetic drug glibenclamide (GLC, 0.6 mg/kg) when administered orally, once daily for 6 days against gastric ulcers (GU) induced by cold-restraint stress (CRS) and ethanol and subsequent changes in gastric mucosal glycoproteins, cell proliferation, free radicals (lipid peroxidation and nitric oxide) and anti-oxidants enzymes (super oxide dismutase and catalase) and glutathione (GSH) levels. MSE showed better ulcer protective effect in NIDDM rats compared with SFT and GLC in CRS-induced GU. NIDDM caused a significant decrease in gastric mucosal glycoprotein level without having any effect on cell proliferation. However, all the test drugs reversed the decrease in glycoprotein level in NIDDM rats, but cell proliferation was enhanced in case of MSE alone. Both CRS or NIDDM as such enhanced gastric mucosal LPO, NO and SOD, but decreased CAT levels while CRS plus NIDDM rats caused further increase in LPO and NO level without causing any further changes in SOD and CAT level. MSE pretreatment showed reversal in the levels of all the above parameters better than GLC. Ethanol caused a decrease in glutathione level which was further reduced in NIDDM-ethanol rats. MSE reversed the above changes significantly in both normal as well as in NIDDM rats, while GLC reversed it only in NIDDM rats. However, SFT was ineffective in reversing the changes induced by CRS or ethanol or when given in NIDDM-CRS or NIDDM-ethanol rats. The results indicated that the ulcer protective effect of MSE could be due to its predominant effect on mucosal glycoprotein, cell proliferation, free radicals and antioxidant systems.

Effect of standardized extract of Ocimum sanctum Linn. on gastric mucosal offensive and defensive factors.

The standardized methanolic extract of leaves of O. sanctum (OSE; eugenol content 5%) given in doses of 50-200 mg/kg, orally, twice daily for five days showed dose-dependent ulcer protective effect against cold restraint stress induced gastric ulcers. Optimal effective dose (100 mg/kg) of OSE showed significant ulcer protection against ethanol and pyloric ligation-induced gastric ulcers, but was ineffective against aspirin-induced ulcers. OSE significantly healed ulcers induced by 50% acetic acid after 5 and 10 days treatment OSE (100 mg/kg) significantly inhibited the offensive acid-pepsin secretion and lipid peroxidation and increased the gastric defensive factors like mucin secretion, cellular mucus, and life span of mucosal cells and had antioxidant effect, but did not induce mucosal cell proliferation. The results indicate that the ulcer protective and healing effects of OSE may be due to its effects both on offensive and defensive mucosal factors.

Effect of Bacopa monniera and Azadirachta indica on gastric ulceration and healing in experimental NIDDM rats.

Gastric ulcers were induced in normal/NIDDM rats by various physical (2 hr cold restraint stress and 4 hr pylorus ligation) and chemical agents (ethanol, 1 ml/200 g, oral, 1 hr before; aspirin, 200 mg/kg, oral, 4 hr) and duodenal ulcers were induced by cysteamine (40 mg/200 g). Ulcer healing activity was studied in gastric ulcers induced by acetic acid (50%) and HCI (0.6 M). The result indicated that in both, normal and NIDDM rats, B. monniera extract (BME, 20-100 mg/kg) did not show any significant effect on blood glucose level, while A. indica (AIE, 250-1000 mg/kg) significantly decreased it. However, both BME (50 mg/kg) and AIE (500 mg/kg) showed significant anti-ulcer and ulcer-healing activities in normal and NIDDM rats. Further, the present results also indicated that the ulcer protective effects of BME was more pronounced in non-diabetic, while that of AIE was more in NIDDM rats. The anti-ulcer and ulcer-healing activities of BME and AIE may be due to their effects on various mucosal offensive and defensive factors, and correction of blood sugar level by AIE may help to have more ulcer protective effect in NIDDM rats.

Oxidative stress and antioxidants status in peptic ulcer and gastric carcinoma.

Oxidative stress is believed to initiate and aggravate many diseases including peptic ulcers and gastric carcinoma. We observed an increase in rat gastric mucosal lipid peroxidation (LPO) and superoxide dismutase (SOD) and a decrease in catalase (CAT) levels in cold restraint stress-induced gastric ulceration while, in clinical peptic ulceration and gastric carcinoma patients, an increase in serum LPO and a tendency to decrease in SOD and CAT levels were observed. The result thus, indicated a positive correlation between free radical-induced oxidative stress both in gastric and duodenal ulcers and gastric carcinoma.

Evaluation of Pongamia pinnata root extract on gastric ulcers and mucosal offensive and defensive factors in rats.

Effect of methanolic extract of P. Pinnata roots (PPRM) was studied against various experimental gastric ulcer models and offensive and defensive gastric mucosal factors in rats. An initial dose-response study using 12.5-50 mg/kg P. Pinnata root extract, when given orally in two divided dose for 4 days + 5th full dose on the day of experiment 60 min before the experiment, indicated 25 mg/kg as an optimal regimen and was used for further study. PPRM showed significant protection against aspirin and 4 hr PL, but not against ethanol-induced gastric ulceration. It showed tendency to decrease acetic acid-induced ulcer after 10 days treatment. Ulcer protective effect of PPRM was due to augmentation of mucosal defensive factors like mucin secretion, life span of mucosal cells, mucosal cell glycoproteins, cell proliferation and prevention of lipid per oxidation rather than on the offensive acid-pepsin secretion.

Antiulcerogenic activity of Satavari mandur--an Ayurvedic herbo-mineral preparation.

Satavari mandur (SM) is a herbo-mineral preparation containing Asparagus racemosus, which finds mention in ancient Indian texts for treatment of gastric ulcers. The ulcer protective effect of SM, 125-500 mg/kg given orally, twice daily for three, five and seven days, was studied on cold restraint stress-induced gastric ulcer in rats. The effective regimen was found to be 250 mg/kg given for five days and hence was used for further experiments. SM showed significant protection against acute gastric ulcers induced by pyloric ligation but was ineffective against aspirin- and ethanol-induced ulcers. Further, gastric juice studies showed that, SM significantly increased the mucosal defensive factors like mucus secretion, but had little or no effect on offensive factors like acid and pepsin secretion.