The ability of benzothiadiazole (BTH) and/or humic acid (HA) used as seed soaking to induce systemic resistance against a pathogenic strain of Fusarium oxysporum was examined in four soybean cultivars under greenhouse conditions. Alone and in combination the inducers were able to protect soybean plants against damping-off and wilt diseases compared with check treatment. These results were confirmed under field conditions in two different locations (Minia and New Valley governorates). The tested treatments significantly reduced damping-off and wilt diseases and increased growth parameters, except the number of branches per plant and also increased seed yield. Application of BTH (0.25 g/L) + HA (4 g/L) was the most potent in this respect. Soybean seed soaking in BTH + HA produced the highest activities of the testes of oxidative enzymes followed by BTH in the four soybean cultivars. HA treatment resulted in the lowest increases of these oxidative enzymes. Similar results were obtained with total phenol but HA increased total phenol more than did BTH in all tested cultivars.
Fusarium ; Phenol ; Plants ; Seeds ; Soybeans ; Sprains and Strains ; Testis ; Thiadiazoles

CLINICAL SCENARIO: A 46-year-old male consulted for refraction. Best-corrected visual acuity was 20/20 for both eyes (OU), Jaeger 1 for near. Slit-lamp examination was normal. Intraocular pressure (IOP) was 25 mm Hg OU. Gonioscopy revealed iridocorneal angles that were open up to the ciliary body band OU. Funduscopy revealed clear media with no exudates or hemorrhages in the retina. Cup-disc ratio was 0.7 vertically and 0.6 horizontally with notching of the inferotemporal neuroretinal rim OU. Automated visual-field examination showed superior arcuate scotomas OU with no threat to fixation. The working diagnosis upon consultation was primary open-angle glaucoma. After all treatment options had been explained to the patient, a trial of medical therapy was chosen. Given the severity of the glaucoma, a target IOP range was initially set at 15 to 17 mm Hg. Nonselective beta-adrenergic blockers and prostaglandin analogues are two classes of medications that will most probably lower the IOP to the desired levels CLINICAL QUESTION: Among patients undergoing initial medical therapy for primary open-angle glaucoma, would latanoprost be more effective in lowering the IOP compared with timolol? SEARCH METHOD: An electronic literature search was performed using Medline (PubMed). The key words used were "latanoprost" and "timolol." The search was further limited to randomized clinical trials or metaanalysis published in the English language. Table 1 shows the search process performed The search was narrowed down to 5 articles. Abstracts of the articles were reviewed. One article employed ocular hypertensive subjects while another compared brimonidine and timolol. These studies were, therefore, excluded. Among all the metaanalyses obtained from the search, Zhang et al.s had the most number of subjects and outcome measures. It was for this reason that the article was chosen for appraisal in resolving the clinical scenario. (Author)
TIMOLOL

To synthesize and evaluate antimicrobial activity of novel heterocyclic compounds, the corresponding title aroyl ureas have been synthesized by the reaction of 2-amino-5-(3-pyridyl)-1, 3, 4-thiadiazole with aroyl isocyanates. Their antimicrobial activities in vitro were tested by disk diffusion methods and broth microdilution according to M-27A protocol recommended by NCCLS. Twelve new compounds were obtained, and their structures were confirmed by MS, IR, 1H NMR and elemental analysis. The biological screening tests showed that most of the compounds have some antifungal activities in vitro. Aroyl ureas incorporating pyridyl thiadiazole ring may be developed as novel antifungal candidate drugs and are worthwhile to be further studied.
Antifungal Agents ; chemical synthesis ; chemistry ; pharmacology ; Candida albicans ; drug effects ; Microbial Sensitivity Tests ; Molecular Structure ; Phenylurea Compounds ; chemical synthesis ; chemistry ; pharmacology ; Thiadiazoles ; chemical synthesis ; chemistry ; pharmacology

Total eight patients(12 eyes) who are suffering from chronic open-angle glaoucoma(7 eyes), Chronic narrow-angle glaucoma (3 eyes) and ocular hypertension (2 eyes) were treated topically with 0.25~0.5% Timoptic ophthalmic solution (Timolol maleate/MSD), and were observed clinically for various periods ranging from 14 days to 120 days. Results are summerized as follows; 1. Timoptic ophthalmic solution is a new effective eye drop to lowering intraocular pressure in patients of open-angle glaucoma and ocular hypertension. We re-comformed its effectiveness on intraocular pressure in Korean glaueoma patients. And its average range for the decrease of intraocular pressure was 8 mmHg (5~12mm Hg). 2. In Chronic narrow-angle glaucoma patients, Timoptic Opthalmic solution could be decreased effectivey intraocular pressure as such as open-angle glaucoma patients. 3. Any other complications such as miosis. irritative hyperemia or tearing etc. were not found during the observation period. 4. In uneffective patients with Timoptic alone, other antiglaucoma agents (pilo., Diamox etc) could be used additively with combination of Timoptic.
Acetazolamide ; Glaucoma, Angle-Closure* ; Glaucoma, Open-Angle ; Humans ; Hyperemia ; Intraocular Pressure ; Miosis ; Ocular Hypertension ; Timolol*

To explore the method of explants directly induced bud and establish the tissue culture system of mutiple shoot by means of direct organogenesis, core bud and daughter bulbs (the top of bud stem expanded to form daughter bulb) of T. edulis were used as explants and treated with thidiazuron (TDZ) and 1-naphthlcetic acid (NAA). The results showed that the optimal medium for bud inducted form core bud and daughter bulb were MS + TDZ 2.0 mg x L(-1) + NAA 4.0 mg x L(-1) and MS +TDZ 2.0 mg x L(-1) + NAA 2.0 mg x L(-1) respectively, both of them had a bud induction rate of 72.92%, 79.22%. The optimal medium for cluster buds multiplication was MS + TDZ 0.2 mg x L(-1) + NAA 0.2 mg x L(-1), and proliferation coefficient was 2.23. After proliferation, cluster buds rooting occurred on MS medium with IBA 1.0 mg x L(-1) and the rooting rate was 52.6%, three to five seedlings in each plant. Using core bud and daughter bulb of T. edulis, the optimum medium for adventitious bud directly inducted from daughter bulb, core bud and cluster bud multiplication were screened out and the tissue culture system of multiple shoot by means of direct organogenesis was established.
Naphthaleneacetic Acids ; pharmacology ; Phenylurea Compounds ; pharmacology ; Plant Growth Regulators ; pharmacology ; Plant Shoots ; drug effects ; growth & development ; Plant Stems ; drug effects ; growth & development ; Seedlings ; drug effects ; growth & development ; Thiadiazoles ; pharmacology ; Tissue Culture Techniques ; Tulipa ; drug effects ; growth & development

To optimize the synthetic method and antibacterial activity of fused heterocyclic thiadiazole compounds, cyclocondensation of 2-(4-methoxyphenyl)-5-amino-1,3,4-thiadiazole (2) with alpha-chloro-4-chloro acetophenone (3) resulted in a key intermediate (4), 6 -(4-chlorophenyl)-2-(4-methoxyphenyl)-imidazo-[2,1-b][1,3,4]thiadiazole, which was carried out an nucleophilic substitution with substituted piperazine to give the corresponding free bases of piperazine (5a-5c), then followed by Mannich reaction with heterocyclicamines and formaldehyde to yield the corresponding Mannich bases, (1a-11) as respective hydrochloride salts. The structures were confirmed by IR, 1H NMR, MS and elemental analysis and the antibacterial activities in vitro of fifteen newly synthesized compounds were also tested against Gram positive bacteria and Gram negative bacteria with the standard 2-fold agar dilution method. The antibacterial results showed that the introduction of a polar group resulted in the enhancement of antibacterial activity in vitro. Thus, the structures of these fused compounds could further be investigated.
Anti-Bacterial Agents ; chemical synthesis ; chemistry ; pharmacology ; Bacillus subtilis ; drug effects ; Escherichia coli ; drug effects ; Imidazoles ; chemical synthesis ; chemistry ; pharmacology ; Mannich Bases ; chemistry ; Microbial Sensitivity Tests ; Molecular Structure ; Pseudomonas aeruginosa ; drug effects ; Staphylococcus aureus ; drug effects ; Thiadiazoles ; chemical synthesis ; chemistry ; pharmacology

OBJECTIVETo explore the tumor growth inhibition of gamma secretase inhibitor MRK003 on human multiple myeloma xenograft mice by inhibition of AKT and Notch1 expression.

METHODSNOD/SCID mice were injected with human multiple myeloma cell lines RPMI8226 to establish a xenograft mouse model. Mice were randomized into two groups：the experimental group were injected with MRK003 at a dose of 5 mg× kg⁻¹×d⁻¹ for 14 days; the inhibitor was replaced by an equal saline in the control group. Mice were sacrificed by cervical dislocation on the next day after the last injection and tumor tissue was removed to detect the expression of Notch1 and AKT by immunohistochemistry.

RESULTSAfter subcutaneous injection with RPMI8226, mice had tumor formation in 5-7 days and the largest tumor block in 10-12 days. Before RPMI8226 injection, the mean sizes of tumor block in the experimental and the control groups were 509.2 mm³, 511.2 mm³(P>0.05). 9 days after injection, the mean sizes of tumor tissue in the experimental and the control groups were 636.6 mm³, 691.2 mm³(P<0.01). On the next day after the last injection, the tumor sizes of the experimental and the control groups were 683.5 mm³ and 1798.7 mm³(P<0.01). The size of tumor block in the experimental group was significantly smaller than that of the control group(P<0.01). Immunohistochemistry staining showed that the positive expression rates of Notch1(11.1%, P<0.01) and AKT(13.3%, P<0.01) in experimental group were significantly decreased compared with the control group(Notch1: 95.6%; AKT: 93.3%). Western blot results showed that Notch1 and AKT protein in experimental group were significantly lower than those in the control group.

CONCLUSIONMRK003 could inhibit the tumor growth of human multiple myeloma xenograft mice by downregulated expression of Notch1 signaling pathway.

Amyloid Precursor Protein Secretases ; antagonists & inhibitors ; Animals ; Cell Line, Tumor ; Cyclic S-Oxides ; pharmacology ; Humans ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Multiple Myeloma ; drug therapy ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Receptor, Notch1 ; metabolism ; Signal Transduction ; drug effects ; Thiadiazoles ; pharmacology ; Xenograft Model Antitumor Assays

OBJECTIVETo characterize the function of a new xanomeline-derived M1 agonist, 3-[3-(3-florophenyl-2-propyn-1-ylthio)-1,2,5-thiadiazol-4-yl]-1,2,5,6- tetrahydro-1-methylpyridine Oxalate (EUK1001), the acute toxicity and the effects on synaptic plasticity and cognition of EUK1001 were evaluated.

METHODSTo examine the median lethal dose (LD50) of EUK1001, a wide dose range of EUK1001 was administered by p.o. and i.p. in aged mice. Furthermore, novel object recognition task and in vitro electrophysiological technique were utilized to investigate the effects of EUK1001 on recognition memory and hippocampal synaptic plasticity in aged mice.

RESULTSEUK1001 exhibited lower toxicity than xanomeline, and improved the performance of aged mice in the novel object recognition test. In addition, bath application of 1 micromol/L EUK1001 directly induced long-term potentiation in the hippocampus slices.

CONCLUSIONWe conclude that EUK1001 can improve the age-related cognitive deficits.

Aging ; drug effects ; Animals ; Brain ; drug effects ; Dose-Response Relationship, Drug ; Excitatory Postsynaptic Potentials ; drug effects ; Lethal Dose 50 ; Long-Term Potentiation ; drug effects ; Memory ; drug effects ; Mice ; Muscarinic Agonists ; administration & dosage ; adverse effects ; Pyridines ; administration & dosage ; adverse effects ; chemistry ; Thiadiazoles ; administration & dosage ; adverse effects ; chemistry

To study the synthetic method and antibacterial activity of water-soluble fused heterocyclic compounds containing piperazine group, the nucleophilic substitution of 3-(4-chlorophenyl)-6-substituted-s-triazolo-[3, 4-b] [1, 3, 4] thiadiazoles (2a - n) with piperazine in the presence of phase transfer catalyst TBAI afforded 3-(4-piperazin-1-yl-phenyl)-6-substituted-s-triazolo [3, 4-b] [1, 3, 4] thiadiazole and then followed by acid treatment afforded 3-(4-piperazin-1-yl-phenyl)-6-substituted-s-triazolo [ 3, 4-b] [1, 3, 4] thiadiazole hydrochlorides (3a - n). Twenty-eight new compounds were synthesized and their structures were confirmed by IR, 1H NMR, MS and element analysis. The in vitro antibacterial activities of all newly synthesized compounds were tested against Gram positive bacteria and Gram negative bacteria with the standard 2-fold agar dilution method. Fourteen title compounds exhibited potential antibacterial activities in vitro. The structures of these compounds needed to be further optimized.
Anti-Bacterial Agents ; chemical synthesis ; chemistry ; pharmacology ; Bacillus subtilis ; drug effects ; Escherichia coli ; drug effects ; Microbial Sensitivity Tests ; Molecular Structure ; Pseudomonas aeruginosa ; drug effects ; Staphylococcus aureus ; drug effects ; Structure-Activity Relationship ; Thiadiazoles ; chemical synthesis ; chemistry ; pharmacology ; Triazoles ; chemical synthesis ; chemistry ; pharmacology

Infantile hemangioma is a common, benign tumor of infancy. Although systemic propranolol was found to be effective in the treatment of infantile hemangioma, its use is often challenging for clinicians owing to its potential side effects. Recent small studies have suggested that the topical use of timolol maleate gel, a non-selective beta-adrenergic antagonist, might be effective for the treatment of superficial infantile hemangioma. Here, we report three cases of infantile hemangioma of different sizes and depths treated with the topical timolol maleate gel-forming solution.
Hemangioma ; Propranolol ; Timolol*