PREDICTION OF THE THERAPEUTIC EFFECTIVENESS OF NEW DRUGS FROM CLINICAL PHARMACOLOGY STUDIES

The development of new drugs for therapeutic purposes has become very expensive and time-consuming in American and European countries.It is estimated that on the average 50 to 100 million dollars and 10 or more years from the time of patenting are required to make a new drug available for general prescription. Every new drug needs to be charac-

Efficacy of Bee Products(Anzer Honey,Pollen and Propolis)in Detection and Healing of Damage Induced by Antidiabetic Drug Vildagliptin/Metformin Hydrochloride in Healthy Human Pancreatic Cells:Cytotoxic,Genotoxic and Biochemical Studies

Background and Objective Although drugs are powerful therapeutic agents,they have a range of side effects.These side effects are sometimes cellular and not clinically noticeable.Vildagliptin/metformin hydrochloride is one of the most widely used oral antidiabetic drugs with two active ingredients.In this study,we investigated its harmful effects on the metabolic activation system in healthy human pancreatic cells“hTERT-HPNE”,and we aimed to improve these harmful effects by natural products.To benefit from the healing effect,we used the unique natural products produced by the bees of the Anzer Plateau in the Eastern Black Sea Region of Turkey.Methods Cytotoxic and genotoxic effects of the drug were investigated by different tests,such as MTT,flow cytometry-apoptosis and comet assays.Anzer honey,pollen and propolis were analyzed by gas chromatography/mass spectrometry(G/C-MS).A total of 19 compounds were detected,constituting 99.9%of the samples.Results The decrease in cell viability at all drug concentrations was statistically significant compared to the negative control(P<0.05).A statistically significant decrease was detected in the apoptosis caused by vildagliptin/metformin hydrochloride with the supplementation of Anzer honey,pollen and propolis in hTERT-HPNE cells(P<0.05).Conclusion This study can contribute to other studies testing the healing properties of natural products against the side effects of oral antidiabetics in human cells.In particular,Anzer honey,pollen and propolis can be used as additional foods to maintain cell viability and improve heal damage and can be evaluated against side effects in other drug studies.

The neuroprotective effects of the anti-diabetic drug linagliptin against Aβ-induced neurotoxicity

Impaired insulin signaling in Alzheimer’s disease（AD）brains：The insulin signaling pathway is a fundamental physiological mechanism that presents in nearly all vertebrate cells.However,sometimes cells stop responding properly to insulin stimulation.This condition is known as insulin resistance,which is a hallmark of two very common conditions,metabolic syndrome and type 2 diabetes（T2D）.

EFFECT OF ANTITUMOR DRUGS ON THE ACTIVITY OF DNA TOPOISOMERASE I

The activity of DNA topoisomerase Ⅱ prepared from either normal or tumor tissues were compared. It was found that the unknotting activity of the enzyme in malignant tumor cells was higher than that in normal cells. We selected some antitumor drugs including Chinese traditional medicine, and observed their effects on the unknotting activity of topoisomerase Ⅱ. The results showed that inhibition of the unknotting activity of the enzyme required very low concentrations of drugs, but much higher concentrations were required for other tested. Some antitumor drugs had no effect on the enzyme were also proved. It is interesting that carrageenan, an antiviral drug, strongly blocked the unknotting activity although its antitumor activity has not been reported.

Late Protective Effects of the Anticalmodulin Drug Fluphenazine on Carbon Tetrachloride-induced Liver Necrosis

Fluphenazine (FP) treatment (50mg/kg bw, ip in saline) 30 min before or 6 or 10 h after CCl4 administration (1 ml/kg ip in olive oil) significantly prevented the liver necrosis produced by the hepatotoxin at 24 h. FP had enhancing effects on the covalent binding of CCl4 reactive metabolites to cellular constituents and on CCl4 induced lipid peroaldation.FP lowered bOdy temperature of the CCl4-poisoned animals during the 24 h observation period. The obtained results are compatible but do not prove the hypothesis that calmodulin (CaM) had participation in late occurring events preceding necrosis. FP lowering action on body temperature, however, might also play a role in the effects of this drug on the onset of CCl4 induced liver necrosis. FP levels in liver tissue as determined by gas chromatography-mass spectrometry evidenced the presence of the drug in amounts suffi cient to inhibit CaM and that suggests that not all preventive effects of FP are due to its indirect actions on the central nervous system via decreased body temperature

Analysis on Therapeutic Effect of Western and Chinese Drug in Treating Intrahepatic Cholestasis of Pregnancy

Objective: To evaluate the therapeutic effect of Yinchenghao decoction (YCHD, 茵陈蒿汤) and S-adenosy-L-methionine (SAM) in treating intra-hepatic cholestasis of pregnancy (TCP) and improving prognosis of perinatal newborn babies. Methods: Sixty in-patients of TCP were randomly divided into two groups, the group A treated with YCHD and the group B treated with SAM. The symptom of itching and serum biochemical indexes, including glycocholic acid, bilirubin and transaminase, were observed after 3 weeks treat-ment, and the prognosis of perinatal newborn babies between the two groups was compared after delivery. Results: After treatment, the symptom of itching, serum levels of glycocholic acid, bilirubin and transaminase improved significantly (P< 0.05) in both groups, and the prognosis of newborn in the two groups was similar (P>0. 05). Conclusion: Both YCHD and SAM could effectively treat ICP. The former is rather cheaper, so it is more feasible for spreading.Original article on CJITWM (Chin) 2004 ;24(4): 309

Effect of Diallyl Trisulfide on Induction of UDS by Mutagenic Drugs in Primary Rat Hepatocytes

Mosl of anticancer drugs are mutagenic. A possible exeeption is diallyl .trisulfide(DAT ), a component of garlic. It is an antimutagenic anticunccr chemical although it ismainly uscd as antibiotic. Its modifying effeci on induction of UDS by mutagenicmitomycin C (MMC), cyclophosphamide (CP) and cis-diamine dichloroplatin (DDP) was invcstigiltcd with the UDS assay in the primary cultures of Wistar rat hepatocytes (hpc)using the autoradiographic technique. Resultsshowed that 1.0-4.0 nmol/ml of DAT didnot inducc UDS and that MMC, CP and DDP resulted in a significant induction ofdosc-dependent UDS. DAT enhanced induction of UDS by these drugs. A dose-effectrclationship was observed betwecn dose of DAT and enhancement of induction of UDS.Howcvcr, thc mcchanism of the enhancement is not clear.

Intellectual Property Protection and High Quality Development of Radix Glycyrrhizae for Treatment of COVID-19

Radix Glycyrrhizae is the dominant native medicinal material variety in the north and northwestern medicinal materials producing areas.It is a main Chinese medicine of effective TCM drugs and formulas for the treatment of new coronavirus disease(COVID-19).This paper introduces the medicinal value of Radix Glycyrrhizae,involving the labeling,cultural heritage,and creative intellectual property rights of the Chinese medicinal materials,analyzes the poverty-stricken areas that are ecologically suitable for Radix Glycyrrhizae cultivation,and the superior counties and production bases of the Chinese medicinal materials.Besides,mainly from the aspects of perfect intellectual property rights,the establishment of authentic medicinal material production bases,and the construction of quality control systems,etc.,it discusses the rural revitalization strategy and the development strategy of traditional Chinese medicine(TCM),agricultural intellectual property protection and high-quality development strategy of Radix Glycyrrhizae.

Design of pharmacodynamic monitoring system based on acupuncture differential thermometry

To control drug effects by detecting temperature difference between biologically active point（BAP）and intact area of skin for treatment of mental illness,a device is developed for monitoring the temperature of BAP and the dose medication and its change in real time to increase effectiveness of treatment.Two electrodes by Foll R method are used and BAP is determined based on topographic anatomical reference points.The temperature values are measured by integral thermometers DS18B20.the received data are processed and temperature difference is calculated and displayed under the control of microcontroller Atmega32.The obtained data confirm the correlation between the temperature difference indicators BAP C7,Gi4 and neurological scales assessing severity of mental illness.The experimetal results show that the temperature difference can be criteria for evaluating the effects of drugs,which is the basis for computer control systems of of medical process of mental patients.

Protective effect of Weikang decoction and partial ingredients on model rat with gastric mucosa ulcer

AIM: To investigate the protective mechanisms of Weikang (WK) decoction on gastric mucosae. METHODS: Ninety rats were randomly divided into nine groups of 10 each, namely group, model group, group with large WK dosage, group with medium WK dosage, group with small WK dosage, group with herbs of jianpiyiqi (strengthening the spleen and replenishing qi), group with herbs of yangxuehuoxue (invigorating the circulation of and nourishing the blood), group with herbs of qingrejiedu (clearing away the heat-evils and toxic materials), group with colloidal bismuth pectin (CBP) capsules. According to the method adopted by Yang Xuesong, except normal control group, chronic gastric ulcer was induced with 100% acetic acid. On the sixth day after moldmaking, WK decoction was administered, respectively at doses of 20, 10 and 5 g/kg to rats of the WK groups, or the groups with herbs of jianpiyiqi, yangxuehuoxue and qingrejiedu, 10 ml/kg was separately administered to each group every day. For the group with CBP capsules, medicine was dissolved with water and doses 15 times of human therapeutic dose were administered (10 mL/kg solution containing 0.35% CBP). Rats of other groups were fed with physiological saline (10 ml/kg every day). Administration lasted for 16 d. Rats were killed on d 22 after mold making to observe changes of gastric mucosa. The mucus thickness of gastric mucosa surface was measured. Levels of epidermal growth factor (EGF) in gastric juice, nitric oxide (NO) in gastric tissue, endothelin (ET) in plasma, superoxide dismutase (SOD) in plasma, malondialdehyde (MDA) in plasma and prostaglandin I2 (PGI2) were examined. RESULTS: Compared with control group, ulceration was found in gastric mucosa of model group rats. The mucus thickness of gastric mucosa surface, the levels of EGF, NO, 6-K-PGF1α and SOD decreased significantly in the model group (EGF: 0.818±0.18 vs 2.168±0.375, NO: 0.213±0.049 vs 0.601±0.081, 6-K-PGF1α 59.7±6.3 vs 96.6±8.30, SOD: 128.6±15.0 vs 196.6±35.3, P<0.01),the levels of ET (179.96±37.40 vs 46.64±21.20, P<0.01) and MDA (48.2±4.5 vs 15.7±4.8, P<0.01) increased. Compared with model group, the thickness of regenerative mucosa increased, glandular arrangement was in order, and cystic dilative glands decreased, while the mucus thickness of gastric mucosa surface increased (20 g/kg WK: 51.3±2.9 vs 23.2±8.4,10 g/kg WK: 43.3±2.9 vs23.2±8.4,, 5 g/kg WK: 36.1±7.2 vs 23.2±8.4, jianpiyiqi: 35.4±5.6 vs 23.2±8.4, yangxuehuoxue: 33.1±8.9 vs 23.2±8.4, qingrejiedu: 31.0±8.0 vs 23.2±8.4 and CBP: 38.2±3.5 vs23.2±8.4, P<0.05-0.01). The levels of EGF (20 g/kg WK: 1.364±0.12 vs 0.818±0.18, 10 g/kg WK: 1.359±0.24 vs 0.818±0.18, 5 g/kg WK: 1.245±0.31 vs 0.818±0.18, jianpiyiqi: 1.025± 0.45 vs 0.818±0.18, yangxuehuoxue: 1.03±0.29 vs 0.818±0.18, qingrejiedu: 1.02±0.47 vs 0.818±0.18 and CBP: 1.237±0.20 VS 0.818±0.18, p<0.05-0.01), NO (20 g/kg WK: 0.480±0.026 vs 0.213±0.049, 10 g/kg WK: 0.390±0.055 vs 0.213±0.049, 5 g/kg WK: 0.394±0.026 vs 0.213±0.049, jianpiyiqi: 0.393±0.123 vs 0.213±0.049, yangxuehuoxue: 0.463±0.077 vs 0.213±0.049, qingrejiedu: 0.382±0.082 vs 50.213±0.049 and CBP: 0.395±0.053 vs 0.213±0.049, P<0.05-0.01), 6-K-PGF1α (20 g/kg WK: 86.8±7.6 vs 59.7±6.3,10 g/kg WK: 77.9±7.0 vs 59.7±6.3, 5 g/kg WK: 70.0±5.4 vs 59.7±6.3, jianpiyiqi: 73.5±12.2 vs 59.7±6.3, yangxuehuoxue: 65.1±5,3 vs 59.7±6.3, qingrejiedu: 76.9±14.6 vs 59.7±6.3,and CBP: 93.7±10.7 vs 59.7±6.3, P<0.05-0.01) and SOD (20 g/kg WK: 186.4±19.9 vs 128.6±15.0,10 g/kg WK: 168.2±21.7 vs 128.6±15.0, 5 g/kg WK: 155.6±21.6 vs 128.6±15.0, jianpiyiqi: 168.0±85.3 vs 128.6±15.0, yangxuehuoxue: 165.0±34.0 vs 128.6±15.0, qingrejiedu: 168.2±24.9 vs 128.6±15.0, and CBP: 156.3±18.1 vs 128.6±15.0, P<0.05-0.01) significantly increased. The levels of ET (20 g/kg WK: 81.30± 17.20 vs 179.96±37.40, 10 g/kg WK: 83.40±25.90 vs 179.96±37.40, 5 g/kg WK: 93.87±20.70 vs 179.96±37.40, jianpiyiqi: 130.67±43.66 vs 179.96±37.40, yangxuehuoxue: 115.88±34.09 vs 179.96±37.40, qingrejiedu: 108.22±36.97 vs 179.96±37.40, and CBP: 91.96±19.0 vs 179.96±37.40, P<0.01) and MDA (20 g/kg WK: 21.6±7.4 vs 48.2±4.5, 10 g/kg WK: 32.2±7.3 vs 48.2±4.5, 5 g/kg WK: 34.2±6.2 vs 48.2±4.5, jianpiyiqi: 34.9±13.8 vs 48.2±4.5, yangxuehuoxue: 35.5±16.7 vs 48.2±4.5, qingrejiedu: 42.2±17.6 vs 48.2±4.5, and CBP: 30.1±6.1 vs 48.2±4.5, P<0.05-0.01) obviously decreased. The 20 g/kg WK group was better than 10 g/kg (the mucus thickness: 51.3±2.9 vs 43.3±2.9, NO: 0.480±0.026 vs 0.390±0.055, SOD: 186.4±19.9 vs 168,2±21.7, P<0.01) and 5 g/kg (the mucus thickness: 51.3±2.9 vs36.1±7.2, NO: 0.480±0.026 vs0.394±0.026, SOD: 186.4±19.9 vs155.6±21.6, P<0.01) groups and CBP group (the mucus thickness: 51.3±2.9 vs 38.2±3.5, NO: 0.480±0.026 vs 0.395±0.053, SOD: 186.4±19.9 vs 156.3±18.1, P<0.01) in the mucus thickness, NO and SOD levels and better than 10 g/kg (86.8±7.6 vs 77.9±7.0, P<0.05) and 5 g/kg (86.8±7.6 vs 70.0±5.4,P<0.05) groups in 6-K-PGF1α level, 10 g/kg WK group was better than 5 g/kg WK (the mucus thickness: 43.3±2.9 vs 36.1±7.2, P<0.01, SOD: 168.2±21.7 vs 155.6±21.6, P<0.05) and CBP groups (the mucus thickness: 43.3±2.9 vs 38.2±3.5, P<0.01, SOD: 168.2±21.7 vs 156.3±18.1, P<0.05) in the mucus thickness and SOD level. In compound group, jianpiyiqi group, yangxuehuoxue group, qingrejiedu group, the level of ET was decreased, NO contents were increased in gastric tissue of ulcers in rats. CONCLUSION: WK decoction and separated recipes have significantly protective effect on ethanol-induced gastric mucosal injury. They can increase the content of EGF in gastric juice, PGI2 SOD in plasma and NO in gastric tissues, thicken the mucus on the gastric mucosa, and decrease the impairing factor MDA, ET in plasma.

Current cancer therapies and their influence on glucose control

This review focuses on the development of hyperglycemia arising from widely used cancer therapies spanning four drug classes.These groups of medications were selected due to their significant association with new onset hyperglycemia,or of potentially severe clinical consequences when present.These classes include glucocorticoids that are frequently used in addition to chemotherapy treatments,and the antimetabolite class of 5-fluorouracil-related drugs.Both of these classes have been in use in cancer therapy since the 1950s.Also considered are the phosphatidyl inositol-3-kinase(PI3K)/AKT/mammalian target of rapamycin(mTOR)-inhibitors that provide cancer response advantages by disrupting cell growth,proliferation and survival signaling pathways,and have been in clinical use as early as 2007.The final class to be reviewed are the monoclonal antibodies selected to function as immune checkpoint inhibitors(ICIs).These were first used in 2011 for advanced melanoma and are rapidly becoming widely utilized in many solid tumors.For each drug class,the literature has been reviewed to answer relevant questions about these medications related specifically to the characteristics of the hyperglycemia that develops with use.The incidence of new glucose elevations in euglycemic individuals,as well as glycemic changes in those with established diabetes has been considered,as has the expected onset of hyperglycemia from their first use.This comparison emphasizes that some classes exhibit very immediate impacts on glucose levels,whereas other classes can have lengthy delays of up to 1 year.A comparison of the spectrum of severity of hyperglycemic consequences stresses that the appearance of diabetic ketoacidosis is rare for all classes except for the ICIs.There are distinct differences in the reversibility of glucose elevations after treatment is stopped,as the mTOR inhibitors and ICI classes have persistent hyperglycemia long term.These four highlighted drug categories differ in their underlying mechanisms driving hyperglycemia,with clinical presentations ranging from potent yet transient insulin resistant states[type 2 diabetes mellitus(T2DM)-like]to rare permanent insulin-deficient causes of hyperglycemia.Knowledge of the relative incidence of new onset hyperglycemia and the underlying causes are critical to appreciate how and when to best screen and treat patients taking any of these cancer drug therapies.

Clinical correlations of infliximab trough levels and antibodies to infliximab in South Korean patients with Crohn's disease

To investigate the clinical implications of infliximab trough levels (IFX-TLs) and antibodies to infliximab (ATI) levels in Crohn’s disease (CD) patients in Asian countries.METHODSIFX-TL and ATI level were measured using prospectively collected samples obtained with informed consent from CD patients being treated at Asan Medical Center, South Korea. We analyzed the correlations between IFX-TLs/ATI levels and the clinical activity of CD (quiescent vs active disease) based on the CD activity index, C-reactive protein level, and physician’s judgment of patients’ clinical status at enrollment. The impact of concomitant immunomodulators was also investigated.RESULTSThis study enrolled 138 patients with CD (84 with quiescent and 54 with active disease). In patients with quiescent and active diseases, the median IFX-TLs were 1.423 μg/mL and 0.163 μg/mL, respectively (P < 0.001) and the median ATI levels were 8.064 AU/mL and 11.209 AU/mL, respectively (P < 0.001). In the ATI-negative and -positive groups, the median IFX-TLs were 1.415 μg/mL and 0.141 μg/mL, respectively (P < 0.001). In patients with and without concomitant immunomodulator use, there were no differences in IFX-TLs (0.632 μg/mL and 1.150 μg/mL, respectively; P = 0.274) or ATI levels (8.655 AU/mL and 9.017 AU/mL, respectively; P = 0.083).CONCLUSIONIFX-TL/ATI levels were well correlated with the clinical activity in South Korean CD patients. Our findings support the usefulness of IFX-TLs/ATI levels in treating CD patients receiving IFX in clinical practice.

Functional magnetic resonance imaging and the brain: A brief review

Functional magnetic resonance imaging(fMRI) is em-ployed in many behavior analysis studies, with blood oxygen level dependent-(BOLD-) contrast imaging being the main method used to generate images. The use of BOLD-contrast imaging in f MRI has been refined over the years, for example, the inclusion of a spin echo pulse and increased magnetic strength were shown to produce better recorded images. Taking careful precautions to control variables during measurement, comparisons between different specimen groups can be illustrated by f MRI imaging using both quantitative and qualitative methods. Differences have been observed in comparisons of active and resting, developing and aging, and defective and damaged brains in various studies. However, cognitive studies using f MRI still face a number of challenges in interpretation that can only be overcome by imaging large numbers of samples. Furthermore, f MRI studies of brain cancer, lesions and other brain pathologies of both humans and animals are still to be explored.

Persistent severe hypomagnesemia caused by proton pump inhibitor resolved after laparoscopic fundoplication

Magnesium deficiency can cause a variety of symptoms, including potentially life-threatening complications such as seizures, cardiac arrhythmias and secondary electrolyte disturbances. Hypomagnesemia can be a serious adverse effect to proton pump inhibitor(PPI) therapy, which is worrying due to the widespread use of PPIs. Current evidence suggest that the mechanism of PPI induced hypomagnesemia is impaired intestinal magnesium absorption. In this report, we present the case of a long-term PPI user with persistent hypomagnesemia with severe symptoms at presentation. He was unable to stop PPI treatment because of severe reflux symptoms, and was dependent on weekly intravenous magnesium infusions, until his magnesium levels finally normalized without the need for supplementation after a successful laparoscopic fundoplication.

Development of ulcerative colitis in a patient with multiple sclerosis following treatment with interferonβ 1a

To alert clinicians to a potential novel adverse drug effect of interferonβ la, we herein report a patient with relapsing-remitting multiple sclerosis who developed ulcerative colitis following treatment with interferonβ la. Ulcerative colitis persisted despite discontinuation of interferonβ la treatment and switching the patient to glatiramer acetate. Tacrolimus （FK506）, 6-mercaptopurine, and prednisolone were required to induce remission. Both ulcerative colitis and multiple sclerosis were eventually well controlled using this regimen. Our report underscores that caution should be exercised when prescribing immunostimulatory agents in patients with inflammatory bowel disease （IBD） and challenges current efforts to stimulate innate immunity as a novel therapeutic concept for IBD.

FIRST STEP VIEW OF THE EFFICACY OF ANTINEOPLASTIC AGENTS

A human K562 leukaemia call and acute adult leudaemia patient samples have been used to test the efficacy of antineoplastic agents with MTT assay.All 18 drugs were invoved.According to the purpose of experiment these durgs were applied at different opportunities or combinations.The drug efficacy has been observed and summarized as four different conditions:1.the change of the time(△ T )closely related with drug effacacy, during the duration the change of drug concentration(△ C) at certain extent has almost no influence; 2the △ C closely related with the efficacy, the △ T has no influence;3. The △ C and △ T effect the results together;and 4.the △ C and △ T effect not the result. And then draw a conclution that the process or drug effacacy has a multiple function with flat distrtct.

Effects of “Caulis Sargentodoxae Formula” on Experimental Endometriosis in Rat

Objective To study the drug effects of ＂Caulis Sargentodoxae Formula＂ which dears away heat and blood clot on experimental endometriosis in rat, and to compare this effect with Danazol＇s effects. Method The model of endometriosis rat was induced by transplanting with endometrium surgically The rats were divided into 6 groups randomly： the non-treatment group, the castrate group, Danazol group（80 mg/kg）, ＂Caulis Sargentodoxae Formula＂ group （110 g/kg）, the medium dose group（77.5 g/kg） and the low dose group（55 g/kg）. After 3 weeks＇ treatment, the volume ofendometrium was detected by cutting the rats＇ belly open, drawing the materials from endometrium for tissue section, and doing the quantity analysis of endometrium by semiautomatic image analysis machine.Results There was no significant difference of the endometrium volumes between the low dose group and the non-treatment group（P〉O.05）, other groups＇ endometrium volumes were significantly lower than those of the non-treatment group（P〈0. 05）. And apart from the low dose group, all other groups＇ heights of the endometrium epithelia were significantly lower than that of the non-treatment group（p〈0.01）. Conclusion ＂Caulis Sargentodoxae Formula＂ can refrain the growth of the endometrium, and the effects are better than that of Danazol＇s.

Improvement of lenvatinib-induced nephrotic syndrome after adaptation to sorafenib in thyroid cancer:A case report

BACKGROUND Target therapy is licensed by United States Food and Drug Administration on certain cancers.Both sorafenib and lenvatinib are tyrosine kinase inhibitor and indicated on radioactive iodine(RAI)-refractory differentiated thyroid cancer(DTC).Lenvatinib is more effective in cancers'control than sorafenib,but causes more nephrotoxicity than sorafenib does.This case is the second published case about the serial adaptions from lenvatinib to sorafenib for improving the proteinuria and,meanwhile,achieving the therapeutic goal.CASE SUMMARY A 56-year-old man suffered from bilateral edematous lower extremities after 1-mo prescription of lenvatinib of 20 mg/d for RAI-refractory DTC.Aside from this symptom,he also developed hypertension.His laboratory showed grade-3 proteinuria(estimated 24-h urine protein:9993 mg),hypoalbuminemia and hypercholesterolemia.Anti-vascular endothelial growth factor(VEGF)therapyinduced nephrotic syndrome was impressed.After reduced dosage of lenvatinib of 10 mg/d and related symptomatic drugs,limited improvement was observed in both adverse effects and caner control.Under this condition,we substituted sorafenib of 400 mg/d for lenvatinib of 10 mg/d.After a 5-mo prescription,not only hypertension and peripheral edema were greatly improved,but also proteinuria was improved from grade three to grade one(estimated 24-h urine protein:962 mg).At the same time the cancer control was achieved,judged from computed tomography and laboratory evidence[thyroglobulin(Tg)before prescription of sorafenib:354.7 ng/m L;Tg after prescription of sorafenib:108.9 ng/m L].CONCLUSION Adaption from lenvatinib to sorafenib is a feasible method to improve the antiVEGF therapy-induced nephrotic syndrome and achieve the therapeutic goal at the same time.

Comparison of Secnidazole and Fenbendazole for the Treatment of Asymptomatic Giardia Infection in Dogs

The objetive of this study was to compare a single dose of secnidazole versus multiple doses of fenbendazole for the treatment of dogs with asymptomatic Giardia infection.Materials and methods:Twenty-four asymptomatic dogs with a positive test result for Giardia spp were randomized in two equal groups to receive a single dose of secnidazole at 30 mg/kg PO,or fenbendazole at 50 mg/kg PO q24h for 3 days.Hematological parameters were evaluated before and 8 days after treatment,and feces were re-examined at days 8,15,and 30 post-treatment by fecal flotation and antigen test.Results:The number of positive dogs in the fenbendazole group was:1(day 8)and 3(days 15 and 30).In the secnidazole group,the number of positive cases were:4(day 8),3(day 15),and 1(day 30).Conclusion:Treatment with secnidazole or fenbendazole,were effective between 75%and 92%to eliminate the excretion of Giardia cysts in canines together with hygienic measures to control,like disinfection with quaternary ammonium of patients and their environment.Further studies that include more animals and multiple fecal exams on consecutive days would be necessary to confirm its efficacy in dogs.