Possible Role of Helicobacter pylori in Ear Nose and Throat Diseases.

Background: Helicobacter pylori is assumed to cause many gastric and extragastric diseases. We aimed to assess the possible association role of H. pylori in Otitis media with effusion (OME), nasal polyps and adenotonsillitis. Patients and Methods: A total of 186 patients with various ear, nose and throat diseases were included. The study comprised 78 children with chronic adenotonsillitis, 43 children with nasal polyps and 65 children with OME. OME patients were assigned to two subgroups: those who have and those who did not have adenoid hyperplasia. Among the patients with bilateral nasal polyps, 20 individuals had recurrent nasal polyps and 23 had de novo nasal polyps. Patients who have chronic adenotonsillitis were divided into three groups: those with chronic tonsillitis and those who underwent tonsillitis, those with chronic adenoiditis and adenoidectomy was performed, and those with chronic adenotonsillitis and underwent adenotonsillectomy. In addition to examination of H. pylori antigen in stool samples of all included patients, real-time polymerase chain reaction (RT-PCR) for detection of H. pylori in the effusion fluid was performed, additionally, Giemsa stain was used for detection of H. pylori organism within the tissue samples when available. Results: Frequency of H. pylori in effusion fluid was 28.6% in patients with OME and adenoid hyperplasia, while in those with OME it was only 17.4% with a p value of 0.2. Nasal polyp biopsies were positive in 13% patients of denovo, and 30% patients with recurrent nasal polyps, p=0.2. De novo nasal polyps were more prevalent in the positive stools than recurrent ones, p=0.7. All adenoid samples were negative for H. pylori, only two samples of tonsillar tissue (8.3%) were positive for H. pylori, and stool analysis was positive in 23 patients with chronic adenotonsillitis. Conclusion: Lack of association between Helicobacter pylori and occurrence of OME, nasal polyposis or recurrent adenotonsillitis.

Possible Role of Ivermectin Mucoadhesive Nanosuspension Nasal Spray in Recovery of Post-COVID-19 Anosmia.

Purpose: Anosmia or hyposmia, with or without taste changes, are common symptoms that occur in SARS-CoV-2 infection and frequently persist as post-COVID-19 manifestations. This is the first trial to assess the potential value of using local ivermectin in the form of a mucoadhesive nanosuspension nasal spray to treat post-COVID-19 anosmia. Methods: It is a controlled, randomized trial. Participants were recruited from South Valley University Hospitals in Qena, Upper Egypt, from the ENT and Chest Diseases Departments and outpatient clinics. Patients with persistent post COVID-19 anosmia were randomly divided into two groups, the first group "ivermectin group" included 49 patients treated by ivermectin nanosuspension mucoadhesive nasal spray (two puffs per day). The second group included 47 patients "placebo group" who received saline nasal spray. Follow- up of anosmia [using Visual analogue scale (VAS)] in all patients for three months or appearance of any drug related side effects was done. Results: The mean duration of pre-treatment post COVID-19 anosmia was 19.5± 5.8 days in the ivermectin group and 19.1± 5.9 days in the placebo group,p˃0.05. Regarding the median duration of anosmia recovery, the ivermectin group recovered from post COVID-19 anosmia in 13 days compared to 50 days in the placebo group, p˂ 0.001. Following the first week of ivermectin nanosuspension mucoadhesive nasal spray therapy, the ivermectin group had a significantly higher percentage of anosmia recovery (59.2%) than the placebo group (27.7%), p˂ 0.01, with no significant differences in recovery rates between the two groups at 1, 2, and 3 months of follow up, p˃0.05. Conclusion: In the small number of patients treated, local Ivermectin exhibited no side effects. In persistent post-COVID-19 anosmia, it could be used for one week at the most as the treatment was extended to one, two and three months, with no difference in recovery compared to the placebo treatment. Trial Registration No: NCT04951362.

Lactoferrin versus Long-Acting Penicillin in Reducing Elevated Anti-Streptolysin O Titer in Cases of Tonsillopharyngitis.

Background: Beta-Hemolytic streptococci are the most frequent bacteria causing tonsillitis. Lactoferrin may play a role in the treatment of chronic tonsillitis due to its direct antimicrobial activity. Objective: To assess the possible role of lactoferrin in reduction of raised serum Anti-Streptolysin O Titer (ASOT) in cases of chronic tonsillopharyngitis in comparison to long acting penicillin. Methods: This study included 117 children with tonsillopharyngitis with high ASOT randomly divided into three groups; group 1 treated with lactoferrin, group 2 treated with long acting penicillin and group 3 treated with both drugs. For all patients ASOT was measured after three and six months of starting treatment. Results: This study included 60 males and 57 females with the mean age (8.5 ± 2.4). There is statistically significant reduction in ASOT in all groups after three months of treatment. ASOT after 3 months was significantly lower in group1 (370±440) and group 3 (350±450) in comparison to group 2 (420±560) with p value 0.02, 0.004, respectively, with no significant difference in comparing group 1 to group 3 p value 0.4. Also, ASO titre after 6 months was significantly lower in group1 (350±420) and group 3 (340±440) in comparison to group 2 (420±550) with p value 0.02, 0.007, respectively, with no significant difference in comparing group 1 to group 3 p value 0.5. In comparing ASOT at three months and six months of treatment in the three studied groups; it decreased by 2% in group 1, and 1.6% in group 3 and no change in group 2. Conclusion: Lactoferrin alone or in combination with long acting penicillin is safe and more effective than long acting penicillin alone in reducing ASOT. Treatment for six months with lactoferrin alone or in combination with long acting penicillin could offer a better response.

Ca2+-dependent modulation of voltage-gated myocyte sodium channels.

Voltage-dependent Na+ channel activation underlies action potential generation fundamental to cellular excitability. In skeletal and cardiac muscle this triggers contraction via ryanodine-receptor (RyR)-mediated sarcoplasmic reticular (SR) Ca2+ release. We here review potential feedback actions of intracellular [Ca2+] ([Ca2+]i) on Na+ channel activity, surveying their structural, genetic and cellular and functional implications, translating these to their possible clinical importance. In addition to phosphorylation sites, both Nav1.4 and Nav1.5 possess potentially regulatory binding sites for Ca2+ and/or the Ca2+-sensor calmodulin in their inactivating III-IV linker and C-terminal domains (CTD), where mutations are associated with a range of skeletal and cardiac muscle diseases. We summarize in vitro cell-attached patch clamp studies reporting correspondingly diverse, direct and indirect, Ca2+ effects upon maximal Nav1.4 and Nav1.5 currents (Imax) and their half-maximal voltages (V1/2) characterizing channel gating, in cellular expression systems and isolated myocytes. Interventions increasing cytoplasmic [Ca2+]i down-regulated Imax leaving V1/2 constant in native loose patch clamped, wild-type murine skeletal and cardiac myocytes. They correspondingly reduced action potential upstroke rates and conduction velocities, causing pro-arrhythmic effects in intact perfused hearts. Genetically modified murine RyR2-P2328S hearts modelling catecholaminergic polymorphic ventricular tachycardia (CPVT), recapitulated clinical ventricular and atrial pro-arrhythmic phenotypes following catecholaminergic challenge. These accompanied reductions in action potential conduction velocities. The latter were reversed by flecainide at RyR-blocking concentrations specifically in RyR2-P2328S as opposed to wild-type hearts, suggesting a basis for its recent therapeutic application in CPVT. We finally explore the relevance of these mechanisms in further genetic paradigms for commoner metabolic and structural cardiac disease.

Therapeutic efficacy of macrolides in management of patients with mild COVID-19.

Evidence on the efficacy of adding macrolides (azithromycin or clarithromycin) to the treatment regimen for COVID-19 is limited. We testify whether adding azithromycin or clarithromycin to a standard of care regimen was superior to standard of supportive care alone in patients with mild COVID-19.This randomized trial included three groups of patients with COVID-19. The azithromycin group included, 107 patients who received azithromycin 500 mg/24 h for 7 days, the clarithromycin group included 99 patients who received clarithromycin 500 /12 h for 7 days, and the control group included 99 patients who received standard care only. All three groups received only symptomatic treatment for control of fever and cough .Clinical and biochemical evaluations of the study participants including assessment of the symptoms duration, real-time reverse transcription-polymerase chain reaction (rRT-PCR), C-reactive protein (CRP), serum ferritin, D-dimer, complete blood count (CBC), in addition to non-contrast chest computed tomography (CT), were performed. The overall results revealed significant early improvement of symptoms (fever, dyspnea and cough) in patients treated with either azithromycin or clarithromycin compared to control group, also there was significant early conversion of SARS-CoV-2 PCR to negative in patients treated with either azithromycin or clarithromycin compared to control group (p < 0.05 for all).There was no significant difference in time to improvement of fever, cough, dyspnea, anosmia, gastrointestinal tract "GIT" symptoms and time to PCR negative conversion between patients treated with azithromycin compared to patients treated with clarithromycin (p > 0.05 for all). Follow up chest CT done after 2 weeks of start of treatment showed significant improvement in patients treated with either azithromycin or clarithromycin compared to control group (p < 0.05 for all).Adding Clarithromycin or azithromycin to the therapeutic protocols for COVID-19 could be beneficial for early control of fever and early PCR negative conversion in Mild COVID-19.Trial registration: (NCT04622891) www.ClinicalTrials.gov retrospectively registered (November 10, 2020).

Primary sinonasal Ewing sarcoma: A case report.

BACKGROUND: Ewing sarcoma (ES) is an aggressive tumour which is typically skeletal in origin. ES involving the head and neck region is uncommon and can be easily confused with other small round blue cell tumours. We herein present a rare case of ES involving the sinonasal area. CASE PRESENTATION: A 5-year-old Somalian boy with no known medical illness presented with progressive nasal blockage associated with clear nasal discharge and intermittent spontaneous epistaxis for three months. CT paranasal sinus and neck region revealed poorly enhancing expansile mass in the right maxillary sinus with areas of necrosis within. Initial radiological differential diagnoses were lymphoma and rhabdomyosarcoma. The mass was biopsied and histologically showed diffuse sheets of small round blue cells that was positive to CD99, NSE and vimentin. The muscle and lymphoid markers were negative. Fluorescence in-situ hybridisation (FISH) study revealed the presence of EWSR1 gene rearrangement thus diagnosis of ES was rendered. CONCLUSIONS: ES of sinonasal tract is a rare entity and its pathological features significantly overlap with others small round blue cells tumour. Demonstration of EWSR1 gene translocation is recommended for the diagnosis of ES particularly at uncommon sites.

Clinical, Biochemical and Molecular Evaluations of Ivermectin Mucoadhesive Nanosuspension Nasal Spray in Reducing Upper Respiratory Symptoms of Mild COVID-19.

BACKGROUND: Ivermectin is an FDA-approved broad-spectrum anti-parasitic agent that has been shown to inhibit SARS-CoV-2 replication in vitro. OBJECTIVE: We aimed to assess the therapeutic efficacy of ivermectin mucoadhesive nanosuspension intranasal spray in treatment of patients with mild COVID-19. METHODS: This clinical trial included 114 patients diagnosed as mild COVID-19. Patients were divided randomly into two age and sex-matched groups; group A comprising 57 patients received ivermectin nanosuspension nasal spray twice daily plus the Egyptian protocol of treatment for mild COVID-19 and group B comprising 57 patients received the Egyptian protocol for mild COVID-19 only. Evaluation of the patients was performed depending on improvement of presenting manifestations, negativity of two consecutive pharyngeal swabs for the COVID-19 nucleic acid via rRT-PCR and assessments of hematological and biochemical parameters in the form of complete blood counts, C-reactive protein, serum ferritin and d-dimer which were performed at presentation and 7 days later. RESULTS: Of the included patients confirmed with mild COVID-19, 82 were males (71.9%) and 32 females (28.1%) with mean age 45.1 ± 18.9. In group A, 54 patients (94.7%) achieved 2 consecutive negative PCR nasopharyngeal swabs in comparison to 43 patients (75.4%) in group B with P = 0.004. The durations of fever, cough, dyspnea and anosmia were significantly shorter in group A than group B, without significant difference regarding the duration of gastrointestinal symptoms. Duration taken for nasopharyngeal swab to be negative was significantly shorter in group A than in group B (8.3± 2.8 days versus 12.9 ± 4.3 days; P = 0.0001). CONCLUSION: Local use of ivermectin mucoadhesive nanosuspension nasal spray is safe and effective in treatment of patients with mild COVID-19 with rapid viral clearance and shortening the anosmia duration. CLINICALTRIALSGOV IDENTIFIER: NCT04716569; https://clinicaltrials.gov/ct2/show/NCT04716569.

Cochlear nerve canal stenosis and associated semicircular canal abnormalities in paediatric sensorineural hearing loss: a single centre study.

OBJECTIVE: This study aimed to evaluate the association between cochlear nerve canal dimensions and semicircular canal abnormalities and to determine the distribution of bony labyrinth anomalies in patients with cochlear nerve canal stenosis. METHOD: This was a retrospective study in which high-resolution computed tomography images of paediatric patients with severe-to-profound sensorineural hearing loss were reviewed. A cochlear nerve canal diameter of 1.5 mm or less in the axial plane was classified as stenotic. Semicircular canals and other bony labyrinth morphology and abnormality were evaluated. RESULTS: Cochlear nerve canal stenosis was detected in 65 out of 265 ears (24 per cent). Of the 65 ears, 17 ears had abnormal semicircular canals (26 per cent). Significant correlation was demonstrated between cochlear nerve canal stenosis and semicircular canal abnormalities (p < 0.01). Incomplete partition type II was the most common accompanying abnormality of cochlear nerve canal stenosis (15 out of 65, 23 per cent). CONCLUSION: Cochlear nerve canal stenosis is statistically associated with semicircular canal abnormalities. Whenever a cochlear nerve canal stenosis is present in a patient with sensorineural hearing loss, the semicircular canal should be scrutinised for presence of abnormalities.

The prevalence of hypersensitivity reactions to snake antivenoms administered in sultanah nur zahirah hospital from 2013 to 2016.

INTRODUCTION: Snakebite is an important medical emergency. Antivenoms remain the only proven treatment for snake envenoming. However, the use of antivenom is associated with hypersensitivity reactions. The aims of this study were to determine the prevalence and types of hypersensitivity reactions and types and outcomes of pharmacological and non-pharmacological treatments for antivenom reactions among snakebite patients that received antivenoms. METHODS: This was a 4-year cross-sectional study of snakebite patients from January 2013 to December 2016 in Hospital Sultanah Nur Zahirah (HSNZ), Terengganu. Data was extracted from the Pharmacy Record on the usage of antivenom and patients of snakebites treated with antivenom were identified. Data of patients were then obtained from the electronic medical records.' Demographic details, clinical features and characteristics of antivenom reactions of patients were recorded in standardized data collection forms and analyzed using chi-square or Mann- Whitney U tests. RESULTS: Of the 44 patients who received antivenom, 24 (54.5%) developed hypersensitivity reaction. All patients developed reaction early. No patient developed delayed (serum-sickness) reaction. Of the 24 patients, 14 (58.3%) had moderate to severe hypersensitivity reaction and 9 (37.5%) patients had mild reactions. Only one (4.2%) patient presented with bradycardia. CONCLUSION: The prevalence of early hypersensitivity reaction to snake antivenom in HSNZ was relatively high. Healthcare providers should be aware of the appropriate method of preparing and administering antivenom, and the management for acute hypersensitivity reactions. This will optimize the management of snakebite and ensure patient safety.

Gating control of the cardiac sodium channel Nav1.5 by its ß3-subunit involves distinct roles for a transmembrane glutamic acid and the extracellular domain.

The auxiliary ß3-subunit is an important functional regulator of the cardiac sodium channel Nav1.5, and some ß3 mutations predispose individuals to cardiac arrhythmias. The ß3-subunit uses its transmembrane α-helix and extracellular domain to bind to Nav1.5. Here, we investigated the role of an unusually located and highly conserved glutamic acid (Glu-176) within the ß3 transmembrane region and its potential for functionally synergizing with the ß3 extracellular domain (ECD). We substituted Glu-176 with lysine (E176K) in the WT ß3-subunit and in a ß3-subunit lacking the ECD. Patch-clamp experiments indicated that the E176K substitution does not affect the previously observed ß3-dependent depolarizing shift of V½ of steady-state inactivation but does attenuate the accelerated recovery from inactivation conferred by the WT ß3-subunit. Removal of the ß3-ECD abrogated both the depolarizing shift of steady-state inactivation and the accelerated recovery, irrespective of the presence or absence of the Glu-176 residue. We found that steady-state inactivation and recovery from inactivation involve movements of the S4 helices within the DIII and DIV voltage sensors in response to membrane potential changes. Voltage-clamp fluorometry revealed that the E176K substitution alters DIII voltage sensor dynamics without affecting DIV. In contrast, removal of the ECD significantly altered the dynamics of both DIII and DIV. These results imply distinct roles for the ß3-Glu-176 residue and the ß3-ECD in regulating the conformational changes of the voltage sensors that determine channel inactivation and recovery from inactivation.

Sickle cell morbidity profile in Omani children.

In order to define the morbidity profile of sickle cell disease in Omani children, we analysed data on 97 children (53 boys, 44 girls) aged < or = 12 years admitted under our care in a regional referral hospital between July 1999 and June 2000. Ninety of them had sickle cell anaemia (HbSS disease) and seven had sickle cell thalassaemia (beta zero). Their mean (SD) steady-state Hb was 7.9 (1.2), range 6-10 g/dl. They were admitted on 316 occasions during the 12-month period. The number of admissions per child ranged from one to 12 (mean 3.3). Vaso-occlusive crises were the main reason for admission (83%), followed by severe anaemia (12%) and infections (4%). During the study period, 31% received blood transfusions. Weight faltering was very common, 68% falling below the 5th percentile of the National Center for Health Statistics reference curves compared with 28% of age- and sex-matched non-sicklers (p < 0.001). Other complications included hypersplenism (four), ischaemic necrosis of the femoral head (two), and one case each of acute chest syndrome, acute splenic sequestration, cholelithiasis and pathological fracture of a lumbar vertebra. Overall, 71% of the children had moderately severe or severe disease. This pattern seems to be attributable, at least in part, to meteorological and genetic factors. The severe morbidity profile reported in this study underscores the need to continue the search for optimal management modalities, including the often emotion-laden issue of prevention.

HIV/AIDS knowledge and attitudes among alcohol and drug abusers in Egypt.

The aim of this study was to assess knowledge, attitudes and practice towards HIV/AIDS among alcohol and drug abusers and the effect of health education (HE) on their knowledge and attitudes. Participants were 265 substance abusers, recruited from 8 addiction rehabilitation centers. A base line study preceding HE was done using a questionnaire composed of five sections. Three scores were developed to assess HIV/AIDS related knowledge. The base line study indicates that addicts with good knowledge scores > or =75%) regarding modes of transmission were significantly higher among males than females. About 70% of the addicts had negative attitudes towards dealing with HIV/AIDS patients, while 55.5% felt sympathy for them. Eleven percent of the injection drug abusers were sharing needle with others, while 38% of the participating females were previously convicted of prostitution. Logistic analysis showed that high level of education was the best predictive variable for good knowledge scores (> or =75%). Evaluation of the health education program revealed a highly significant increase in the knowledge scores among both males and females compared to the pretest scores. An increase in the percentages of male and female addicts with improved attitudes towards HIV/AIDS patients was also noted after HE. So, HE was found to be a successful tool in improving the knowledge and attitudes of substance abusers towards HIV/AIDS.

A molecular defect in hepatic cholesterol biosynthesis in sitosterolemia with xanthomatosis.

We examined the relationship between cholesterol biosynthesis and total and high affinity LDL binding in liver specimens from two sitosterolemic and 12 healthy control subjects who died unexpectedly and whose livers became available when no suitable recipient for transplantation was identified. Accelerated atherosclerosis, unrestricted intestinal sterol absorption, increased plasma and tissue plant sterol concentrations, and low cholesterol synthesis characterize this disease. Mean total microsomal HMG-CoA reductase (rate-control controlling enzyme for cholesterol biosynthesis) activity was sevenfold higher (98.1 +/- 28.8 vs. 15.0 +/- 2.0 pmol/mg protein per min) and microsomal enzyme protein mass was eightfold larger (1.43 +/- 0.41 vs. 0.18 +/- 0.04 relative densitometric U/mg protein) in 11 controls than the average for two sitosterolemic liver specimens. HMG-CoA reductase mRNA probed with pRED 227 and pHRED 102 was decreased to barely detectable levels in the sitosterolemic livers. In addition, there was a 50% decrease in the rate [2-14C]mevalonic acid was converted to cholesterol by sitosterolemic liver slices compared with controls (112 vs. 224 +/- 32 pmol/g liver per h). In contrast, average total LDL binding was 60% greater (326 vs. 204 +/- 10 ng/mg), and high affinity (receptor-mediated) binding 165% more active (253 vs. 95.1 +/- 8.2 ng/mg) in two sitosterolemic liver membrane specimens than the mean for 12 controls. Liver morphology was intact although sitosterolemic hepatocytes and microsomes contained 24 and 14% less cholesterol, respectively, and 10-100 times more plant sterols and 5 alpha-stanols than control specimens. We postulate that inadequate cholesterol biosynthesis is an inherited abnormality in sitosterolemia and may be offset by augmented receptor-mediated LDL catabolism to supply cellular sterols that cannot be formed.

Feedback regulation of bile-acid synthesis in the rat. Differing effects of taurocholate and tauroursocholate.

We studied the effect of the orientation of the 7-hydroxyl group in taurocholate (7 alpha) and tauroursocholate (7 beta) on the feedback regulation of bile-acid synthesis and its rate-controlling enzyme, cholesterol 7 alpha-hydroxylase, in bile-fistula rats. To ensure a constant supply of cholesterol and to label newly synthesized bile acids, RS[2-14C]mevalonolactone was infused intraduodenally at 154 mumol/h before and during bile-acid infusion. Mevalonolactone inhibited hydroxymethyl-glutaryl CoA reductase activity 90% but did not increase bile-acid synthesis and cholesterol 7 alpha-hydroxylase activity. When sodium taurocholate was infused at the rate of 27 mumol/100 g rat per h (equivalent to the hourly hepatic bile-acid flux), bile-acid synthesis decreased 82% and cholesterol 7 alpha-hydroxylase activity declined 78%. This inhibitory effect was observed in the absence of hepatic damage. In contrast, sodium tauroursocholate infused at the same rate did not decrease bile-acid synthesis nor cholesterol 7 alpha-hydroxylase activity. Hepatic cholesterol content rose 36% with sodium taurocholate but did not change during sodium tauroursocholate administration. These results demonstrate that the feedback inhibition of bile-acid synthesis is mediated through the regulation of cholesterol 7 alpha-hydroxylase. In these experiments, taurocholate was a far more potent inhibitor than its 7 beta-hydroxy epimer, tauroursocholate.

Comparative effects of cholestanol and cholesterol on hepatic sterol and bile acid metabolism in the rat.

Large amounts of cholestanol, the 5 alpha-dihydro derivative of cholesterol are found in tissues of patients with the rare inherited sterol storage disease cerebrotendinous xanthomatosis. Although small amounts of cholestanol are present in virtually every tissue of normal man, little is known about its metabolism and effect on cholesterol and bile acid formation. The purpose of this study is to investigate the absorption and metabolism of cholestanol and its early effects on hepatic morphology and on the rate-limiting enzymes of cholesterol and bile acid biosynthesis. After 2 wk on a diet supplemented with 2% cholestanol, total liver sterol content increased by 48% (3.26 vs. 2.20 mg/g), and resulted in a significant rise in hepatic cholestanol concentration to 1.4 mg/g. However, cholestanol was less efficiently absorbed from the intestine than cholesterol and interfered with cholesterol absorption. Furthermore, hepatic hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase activity rose 2.6-fold (from 150.3 to 397.0 pmol/mg per min) during cholestanol feeding, and was associated with a marked proliferation of the smooth endoplasmic reticulum of the centrilobular areas. In addition, significant amounts of allocholic acid (16%) and allochenodeoxycholic acid (5%) were formed from cholestanol and excreted in the bile. These results show that cholestanol is absorbed from the intestine, interferes with cholesterol absorption, and is deposited in the liver. However, in contrast to cholesterol, cholestanol feeding was associated with a marked elevation of HMG-CoA reductase activity. Thus, despite structural similarity between cholesterol and its 5 alpha-saturated derivative, cholestanol does not exert feedback inhibition on hepatic cholesterol biosynthesis.

Early morphologic and enzymatic changes in livers of rats treated with chenodeoxycholic and ursodeoxycholic acids.

The effect of high doses of chenodeoxycholic and ursodeoxycholic acids on hepatic morphology and on cholesterol and bile acid metabolism was examined in the rat. After 2 weeks of either cheno or ursodeoxycholic acid feeding, the livers of the treated rats revealed marked proliferation of the smooth endoplasmic reticulum which appeared as an adaptation phenomenon of the microsomal enzyme system in response to bile acid intake. However, the livers of the chenodeoxycholic acid-treated rats showed early alteration that included mild triaditis, swelling of the bile canalicular microvilli, distended Golgi vesicles, whorling of the mitochondria, and presence of large vacuoles bound by single membranes. During cheno- or ursodeoxycholic acid treatment, the administered bile acid predominated in the bile and amounted to 79 or 67% of the biliary bile acids, respectively. At the same time, the concentration of the muricholic acids was also increased. Biliary cholic acid content dropped significantly, but no change in lithocholic acid concentration was observed. In addition, the activity of HMG-CoA reductase as well as that of cholesterol-7 alpha-hydroxylase was reduced by either of the administered bile acids, while no change in hepatic cholesterol content was detected, and intestinal cholesterol absorption was not significantly different from that of controls. These results show that cheno- and ursodeoxycholic acids inhibited hepatic cholesterol and bile acid synthesis but did not increase either intestinal cholesterol absorption or hepatic microsomal cholesterol content. Since the amounts of biliary lithocholic acid were similar in the bile acid-treated animals, the morphologic abnormalities detected in the chenodeoxycholic acid-fed rats are probably due to an increased pool of chenodeoxycholic acid. However, lithocholic acid-induced liver injury cannot be excluded.

Serum and hepatic enzyme activity in rats treated with diethylnitrosamine.

Comparative studies of enzyme activities during the dedifferentiation of hepatic cells and through their development into overt hepatomas are few and contradictory. This study was designed to investigate the histochemical, biochemical and morphologic features of the altered liver cells with particular emphasis on the importance and validity of the histoenzymatic behavior of glucose-6-phosphatase (G6Pase) as a marker for the detection of precancerous hepatic cells. Serum and hepatic levels of G6Pase were analyzed and compared with the histoenzymatic behavior of this enzyme. The use of other enzymes, such as adenosine triphosphatase (ATPase) and gamma glutamyl-transpeptidase (GGT) as histochemical markers for malignancy was also tested. The activities of a variety of enzymes commonly used as diagnostic tools were also evaluated in both the liver homogenates and sera of rats treated with 2 mg diethylnitrosamine (DENA)/kg body weight for 2-28 weeks. Using G6Pase as a histoenzymatic marker, precancerous cells appeared after 4 weeks of exposure to DENA in the form of small islets devoid of G6Pase activity. These G6Pase free cells increased in number forming larger islands and finally appeared as tumor nodules after 28 weeks of treatment. The histoenzymatic behavior of ATPase was identical to that of G6Pase. The precancerous cells, as well as the tumor cells appeared devoid of ATPase activity. The application of GGT as a marker, showed significantly increased activity in the altered liver and tumor cells. Increased serum levels of G6Pase were noted after 10 weeks and were greatly elevated in the late stages of the evolution of the precancerous cells.(ABSTRACT TRUNCATED AT 250 WORDS)