Short-term results of changes in existing and de novo lower urinary tract symptoms after robot-assisted laparoscopic uterosacral ligament suspension and sacrocolpopexy.

OBJECTIVE: This study presents short-term outcomes related to changes in existing and de novo lower urinary tract symptoms (LUTS), pelvic pain, and bowel function following robot-assisted laparoscopic uterosacral ligament suspension (RALUSLS) and sacrocolpopexy (RALSC). METHODS: Observational data for RALUSLS (n = 23) and RALSC (n = 25) collected between August 2014 and March 2016 from a single institute (The University of Texas Medical Branch) were evaluated retrospectively. Patient characteristics, concomitant procedures, and the occurrence of lower urinary tract, pelvic pain, and bowel symptoms were compared between patients undergoing RALUSLS and RALSC. RESULTS: There was no significant difference in background characteristics between the 2 groups, except for parity, which was high in the RALUSLS group. In the RALUSLS group, patients experienced significant resolution of urinary urgency (P < .001) and frequency, urge and mixed incontinence, and pelvic pain (P < .05). In the RALSC group, there was significant resolution of nocturia, mixed incontinence, pelvic pain, and dyspareunia (P < .05). There was no significant difference in the occurrence of de novo symptoms in the RALUSLS and RALSC groups (P > .05), although newly appearing urinary urgency or frequency and stress or urge incontinence were more common after RALSC. CONCLUSION: Mixed incontinence and pelvic pain improved significantly in patients after RALUSLS or RALSC. In RALUSLS patients, urgency, frequency, and urge incontinence also improved, whereas additional improvement in nocturia and dyspareunia was evident only in RALSC patients. De novo LUTS developing after these procedures, especially after RALSC, necessitate careful patient consultation prior to surgery.

Short-term results of the efficacy of percutaneous tibial nerve stimulation on urinary symptoms and its financial cost.

OBJECTIVE: Overactive bladder (OAB) affects 16.9% of women in the United States. Percutaneous tibial nerve stimulation (PTNS) is a third-line treatment for patients who are refractory to behavioral and pharmacologic therapies. We aimed to evaluate the effects of PTNS on urinary symptoms in patients diagnosed as having refractory OAB and investigate the cost of medications and clinical visits before and after PTNS treatment. MATERIAL AND METHODS: We reviewed 60 women with refractory OAB treated with PTNS. Episodes of urinary frequency, leakage, urgency, and nocturia; number of follow-up visits; and medications were recorded. The mean quarterly drug, physician, nurse, and provider costs were calculated. The episodes of urinary symptoms, numbers of follow-up visits, and costs of medications and visits before and after PTNS were compared. RESULTS: Of the 60 patients with refractory OAB, 24 patients who completed 12 weekly sessions of initial PTNS were evaluated. The number of urinary symptoms and follow-up visits significantly decreased after PTNS (p<0.05). The average quarterly medication cost decreased from $656.36±292.45 to $375.51±331.79 after PTNS (p=0.001). After PTNS, quarterly physician and nurse visit costs decreased from $81.73±70.39 to $25.89±54.40 and from $55.23±38.32 to $15.53±19.58, respectively (p<0.05). The quarterly total provider cost was similar before and after PTNS. CONCLUSION: PTNS treatment significantly improved urinary symptoms of patients with refractory OAB and reduced the costs of medications and physician and nurse visits.

Rare complication of needleless mini-sling procedure: Case report.

The mini-sling procedure is a widely used, minimally invasive treatment for stress urinary incontinence. While bladder perforation and stone formation over the mesh is not an expected complication of the mini-sling procedure, in this case, we report on the management of bladder calculi formed over the mesh, which was passed through the bladder while applying the mini-sling procedure, and was eventually removed using holmium laser. Performing cystoscopy in patients with irritative and obstructive symptoms after the sling procedure will help confirm bladder perforation, and an endoscopic approach using holmium laser is an effective treatment.

Marginally designed new profen analogues have the potential to inhibit cyclooxygenase enzymes.

The current structure-activity relationship of profens (i.e., 2-arylpropionic acid derivatives, a class of non-steroidal anti-inflammatory drugs) discusses the importance of α-monomethyl substitution on these compounds, since the activities obtained through their corresponding arylacetic acid derivatives (i.e., α-demethylated derivatives) or α,α-dimethyl-substituted compounds are less than what is observed for the parent profens. Unfortunately, this implies a generalization in structure-activity relationships of profens in such a way that a mono-(non-methyl)alkyl group or dialkyl substituent replaced at the α-position of a profen analogue results in abolished activity. Therefore, within this study, we aimed to question this generalization employing ibuprofen, flurbiprofen, and naproxen as model compounds. A series of α-(non-methyl)alkyl-substituted ibuprofen and flurbiprofen analogues as well as α,α-dialkyl-substituted ibuprofen, flurbiprofen, and naproxen derivatives were synthesized and screened for their potential to inhibit cyclooxygenase enzymes. In addition, since profens have negligible potential to inhibit lipoxygenase enzymes, the effect of such derivatization was also questioned in lipoxygenase inhibition assays. The findings only partially agreed with the current structure-activity approach of profens and the activity results of some compounds were found as beyond ordinary.

Design, synthesis and biological evaluation of novel 6H-benzo[c]chromen-6-one, and 7,8,9,10-tetrahydro-benzo[c]chromen-6-one derivatives as potential cholinesterase inhibitors.

Hydroxylated 6H-benzo[c]chromen-6-one derivatives (i.e., urolithins) are the main bioavailable metabolites, and biomarkers of ellagitannins present in various nutrition. Although these dietaries, the sources of urolithins, are employed in folk medicine as cognitive enhancer in the treatment of Alzheimer's Disease, urolithins have negligible potential to inhibit acetylcholinesterase and butyrylcholinesterase enzymes, the validated targets of Alzheimer's Disease. Therefore, within this research, a series of 6H-benzo[c]chromen-6-one, and 7,8,9,10-tetrahydro-benzo[c]chromen-6-one derivatives has been designed, synthesized, and their biological activities were evaluated as potential acetylcholinesterase and butyrylcholinesterase inhibitors. The compounds synthesized exerted comparable activity in comparison to rivastigmine, galantamine, and donepezil both in in vitro and in vivo studies.

Is three-dimensional prenatal ultrasound necessary: pregnant women's point of view.

OBJECTIVES: The role and applicability of three-dimensional ultrasound (3D-US) in perinatology has been repeatedly discussed in the literature. Regardless, our knowledge about patient expectations remains limited. We aimed at determining the expectations, perception and knowledge of pregnant women about 3D-US. MATERIAL AND METHODS: Upon admission to the labor unit, the women filled out a questionnaire, with the help of a doctor investigating sociodemographic data, pregnancy and delivery history previous experiences and expectations for US imaging. RESULTS: A total of 644 pregnant women were included in the study Respondents declared that approximately 70% of all kinds of structural abnormalities could be detected by 3D-US and estimated its reliability at nearly 70%. While 60% of the participants underwent 3D-US, 70% of them believed that every pregnant woman should undergo such test. Also, 457 (70.9%) of the participants were of the opinion that every pregnant woman must undergo 3D-US imaging, whereas 173 (26.8%) did not think 3D-US imaging was necessary CONCLUSIONS: To the best of our knowledge, this has been the first study on patient opinions regarding the need for 3D-US imaging during pregnancy Although the participants were not certain about the harmful effects of 3D-US, the majority believed that it was necessary for every pregnant woman to undergo such testing. Obviously patients must be instructed on the limitations of US imaging before the examination to clarify any misunderstandings about the possibilities such a technique may offer

The relationship between third trimester maternal hemoglobin and birth weight/length; results from the tertiary center in Turkey.

OBJECTIVE: The aim of this study was to investigate the relationship between third trimester maternal hemoglobin values and fetal birth weight/length. METHODS: Retrospective study was conducted on 28600 Turkish pregnant women who delivered between January 2010 and December 2011. Hemoglobin values at third trimester, all birth weights/lengths of newborns were retrospectively analyzed. Maternal third trimester hemoglobin values and birth weights/lengths were compared and correlated. RESULTS: The high hemoglobin concentrations at third trimester were associated with high birth weight (odds ratio 1.08; 95% confidence interval 1.05-1.11; p=0.00) and significant positive correlation was determined between maternal third trimester hemoglobin and birth weights/lengths (p=0.00). Low hemoglobin was associated with low length of newborns (p=0.00). CONCLUSIONS: The low hemoglobin values at third trimester gestation were associated with low birth weight and length in Turkish women. The anemia can be a direct cause of deterioration of in utero fetal growth due to lack of oxygen flow to placental tissue or can be an indirect indicator of maternal nutrition deficit. In both circumstances this study reveals that treatment of anemia is directly correlated with better fetal outcomes.

Synthesis, biological evaluation, and docking studies of novel heterocyclic diaryl compounds as selective COX-2 inhibitors.

Three novel series of diaryl heterocyclic derivatives bearing the 2-oxo-5H-furan, 2-oxo-3H-1,3-oxazole, and 1H-pyrazole moieties as the central heterocyclic ring were synthesized and their in vitro inhibitory activities on COX-1 and COX-2 isoforms were evaluated using a purified enzyme assay. The 2-oxo-5H-furan derivative 6b was identified as potent COX inhibitor with selectivity toward COX-1 (COX-1 IC(50)=0.061 microM and COX-2 IC(50)=0.325 microM; selectivity index (SI)=0.19). Among the 1H-pyrazole derivatives, 11b was found to be a potent COX-2 inhibitor, about 38 times more potent than Rofecoxib (COX-2 IC(50)=0.011 microM and 0.398 microM, respectively), but showed no selectivity for COX-2 isoform. Compound 11c demonstrated strong and selective COX-2 inhibitory activity (COX-1 IC(50)=1 microM, COX-2 IC(50)=0.011 microM; SI= approximately 92). Molecular docking studies of compounds 6b and 11b-d into the binding sites of COX-1 and COX-2 allowed to shed light on the binding mode of these novel COX inhibitors.

Synthesis and biological evaluation of 4,5-diphenyloxazolone derivatives on route towards selective COX-2 inhibitors.

A series of 3-unsubstituted/substituted-4,5-diphenyl-2-oxo-3H-1,3-oxazole derivatives were prepared as selective cyclooxygenase-2 (COX-2) inhibitors. Among the synthesized compounds, 4-(4-phenyl-3-methyl-2-oxo-3H-1,3-oxazol-5-yl)benzensulfonamide (compound 6) showed selective COX-2 inhibition with a selectivity index of >50 (IC(50)COX-1=>100 microm, IC(50)COX-2=2 microm) in purified enzyme (PE) assay. Compound 6 also exhibited selective COX-2 inhibition in human whole blood assay. Molecular docking studies showed that 6 can be docked into the COX-2 binding site thus providing the molecular basis for its activity.

Synthesis, characterization and preliminary screening of regioisomeric 1-(3-pyridazinyl)-3-arylpyrazole and 1-(3-pyridazinyl)-5-arylpyrazole derivatives towards cyclooxygenase inhibition.

In a search for novel compounds with analgesic and anti-inflammatory activity, a series of regioisomeric 1-(3-pyridazinyl)-3-arylpyrazole (5a-f, 6a-f) and 1-(3-pyridazinyl)-5-arylpyrazole (7a-f, 8a-f) derivatives were synthesized. The structure of these regioisomers was confirmed by spectral techniques. The compounds were preliminarily screened at 8 microM concentration for their inhibitory activity against cyclooxygenase enzymes, COX-1 and COX-2, using a human whole blood test. The tested derivatives showed inhibitory activity for both enzymes and are worthy of further investigation for developing better leads.

Synthesis and analgesic activity of some 4,6-disubstituted-3(2H)-pyridazinone derivatives.

A series of 6-morpholino-4-aryl-3(2H)-pyridazinone alkanoic acids, their ester and amide derivatives were prepared and tested for their in vivo analgesic activity by using the p-benzoquinone-induced writhing test. The analgesic activity of the compounds 6-morpholino-4-aryl-3(2H)-pyridazinone (6a-b) were comparable but little lower than that of acetyl-salicylic acid (CAS 50-78-2) as an analgesic agent. The 6-morpholino-4-aryl-3(2H)-pyridazinones having a propanoic acid (10a-b), ester (7a) and amides (12a-b, 12d and 12g) as side chains at the position 2 of the pyridazinone ring showed higher activity than the reference compound without gastric ulceration forming potential. All other compounds generally showed higher activity but caused gastric ulceration in the animals.

Effects of caffeic acid phenethyl ester on lipopolysaccharide-induced lung injury in rats.

Extracts of propolis, a natural beehive product, have been known for centuries to have a variety of beneficial medical properties, among which their anti-inflammatory effect is a major one. Caffeic acid phenethyl ester (CAPE), an active propolis component, has antimicrobial, anti-inflammatory, antioxidant, carcinostatic and immunomodulatory properties. In this study, we aimed to investigate the efficacy of CAPE in endotoxin-induced lung injury in rats. Lung injury was induced by a footpad injection of lipopolysaccharide (LPS). In the treatment group, 10 micromol kg(-1) CAPE was injected intraperitoneally immediately after LPS injection. At 24 h after LPS and/or CAPE injection, blood and lung tissue specimens were collected. MDA levels and MPO activity in serum and lung tissue, serum total antioxidant levels, lung tissue Na(+)/K(+) ATP-ase activity and histopathological evaluation were determined to assess the efficacy of CAPE treatment. CAPE was found to be efficient in reducing inflammation and lung tissue damage induced by LPS in rats.

Synthesis of amide derivatives of [6-(3,5-dimethylpyrazol-1-yl)-3(2H)-pyridazinone-2-yl] acetic acid and their analgesic and anti-inflammatory properties.

A series of structurally different amide derivatives of [6-(3,5-dimethylpyrazol-1-yl)-3(2H)-pyridazinone-2-yl]acetic acid were prepared and tested for their analgesic and anti-inflammatory activity in vivo by using p-benzoquinone-induced writhing test and carrageenan-induced hind paw edema model, respectively. The analgesic and anti-inflammatory activity of the compounds 6a and 6b were equipotent, and 6m was more potent than acetyl salicylic acid (CAS 50-78-2) as an analgesic and indometacin (CAS 53-86-1) as an anti-inflammatory drug, respectively. The other amide derivatives and parent carboxylic acid molecule generally resulted in lower activity to reference compounds. Inhibitor activity of the active compounds on cyclooxygenase isoforms was also investigated by using in vitro COX inhibitor screening assay and found that these derivatives did not exert their analgesic and anti-inflammatory activities through COX inhibition and that other mechanisms might be involved.

Synthesis, analgesic, and anti-inflammatory activities of [6-(3,5-dimethyl-4-chloropyrazole-1-yl)-3(2H)-pyridazinon-2-yl]acetamides.

A series of structurally diverse amide derivatives of [6-(3,5-dimethyl-4-chloro-pyrazole-1-yl)-3(2H)-pyridazinone-2-yl]acetic acid were prepared and tested for their in vivo analgesic and anti-inflammatory activity by using p-benzoquinone-induced writhing test and carrageenan-induced hind paw edema model, respectively. The analgesic and anti-inflammatory activity of the compounds, 7c, 7d and 7k were found to be equipotent to aspirin (as an analgesic) and indometacin (as an anti-inflammatory drug), respectively. The other amide derivatives generally resulted in lower activity on comparision with reference compounds.

Amide derivatives of [6-(5-methyl-3-phenylpyrazole-1-yl)-3(2H)-pyridazinone-2-yl]acetic acids as potential analgesic and anti-inflammatory compounds.

In this study, amide derivatives of [6-(5-methyl-3-phenyl-pyrazole-1-yl)-3(2H)-pyridazinone-2-yl]acetic acid were synthesized and tested for their in vivo analgesic and anti-inflammatory activity by using the p-benzoquinone-induced writhing test and carrageenan-induced hind paw edema model, respectively. The analgesic and anti-inflammatory activity of the compounds 6a, 6d, 6e, 6g, 6h and 6m were more potent than that of aspirin as an analgesic and indomethacin as an anti-inflammatory drug, respectively. The other derivatives generally resulted in comparable activity to reference compounds. Inhibitor activity of the active compounds on cyclooxygenase isoforms was also investigated by using in vitro human whole blood assay and found that these derivatives did not exert their analgesic and anti-inflammatory activities through COX inhibition and other mechanisms might be involved.

4-(5-chloro-2(3H)-benzoxazolon-3-yl) butanoic acid derivatives: synthesis, antinociceptive and anti-inflammatory properties.

In this study, 4-(5-chloro-2(3H)-benzoxazolone-3-yl)butanoic acid and its ethyl ester as well as its ten new amide derivatives have been synthesized. Their structures have been elucidated by IR, (1)H-NMR spectra and elemental analysis. The compounds were screened for antinociceptive and anti-inflammatory activities. The highest antinociceptive and anti-inflammatory activities were exhibited by Compound 11 which has carboxylic acid structure. A various decrease in antinociceptive and anti-inflammatory activity was observed by amidation of the carboxylic acid moiety of this compound.

Investigations of new pyridazinone derivatives for the synthesis of potent analgesic and anti-inflammatory compounds with cyclooxygenase inhibitory activity.

In this study we describe the synthesis of two novel 4-phenyl-and 4-(2-chlorophenyl)-6-(5-chloro-2-oxo-3H-benzoxazol-7-yl)-3(2H)-pyridazinone derivatives (compounds 8a and b) and their testing as inhibitors of cyclooxygenases (COX-1 and COX-2). Both compounds inhibited COX-1 (by 59 % and 61 % for compounds 8a and 8b respectively and COX-2 (by 37 % and 28 % for compounds 8a and 8b respectively) at a concentration of 10 microM. Furthermore, we tested the analgesic and anti-inflammatory activities of the synthesized compounds in vivo by using the p-benzoquinone-induced writhing test and the carrageenan-induced hind paw edema model, respectively. Compounds 8a and 8b showed potent analgesic and anti-inflammatory activities without causing gastric lesions in the tested animals.

Studies on novel 7-acyl-5-chloro-2-oxo-3H-benzoxazole derivatives as potential analgesic and anti-inflammatory agents.

In this study, a series of (7-acyl-5-chloro-2-oxo-3H-benzoxazol-3-yl)alkanoic acid derivatives were synthesized and evaluated for their analgesic and anti-inflammatory activities by using the p-benzoquinone-induced writhing test and the carrageenan hind paw edema model, respectively. Acetic acid-induced peritoneal capillary permeability test and serotonin-induced hind paw edema test were also employed for the most active compounds. The test results indicated that (7-acyl-2-oxo-3H-benzoxazol-3-yl)alkanoic acids (Compounds 6 a-c, 8 a-c, 10 a-c) were equally or more potent analgesic and anti-inflammatory agents than aspirin and indomethacin respectively. The compounds 8a and 8c, but not 8b have the longest carbon chain on alkanoic acid moiety did not induce gastric lesion in mice.

Synthesis and analgesic and anti-inflammatory activity of some new (6-acyl-2-benzoxazolinone and 6-acyl-2-benzothiazolinone derivatives with acetic acid and propanoic acid residues.

In this study for developing potent analgesic and anti-inflammatory compounds, we synthesized 6-acyl-2-benzoxazolinone and 6-acyl-2-benzothiazolinone derivatives with acetic acid and propanoic acid side chain, and performed preliminary screening of their in vivo analgesic and anti-inflammatory activities at a single dose of 100 mg/kg inmice by a p-benzoquinone-induced writhing test and a Carrageenaninduced hind paw edema model, respectively. We also determined their gastric ulceration effects in the tested animals. Propanoic acid derivatives were generally found to have higher analgesic and anti-inflammatory activities, and among them, 3-(6-benzoyl-2-benzothiazolinon-3-yl)propanoic acid (Compound 4 a) exhibited the highest analgesic and anti-inflammatory activity. However, all compounds showed lower anti-inflammatory effects than we observed for indomethacin at 10 mg/kg dose. Consequently, 6-acyl-2-benzoxazolinone/2-benzothiazolinones having propanoic acid side chain might lead to further studies for developing better candidates with potent analgesic and anti-inflammatory effects while acetic acid derivatives do not exhibit comparable satisfactory features.

Amide derivatives of [5-chloro-6-(2-chloro/fluorobenzoyl)-2-benzoxazolinone-3-yl]acetic acids as potential analgesic and anti-inflammatory compounds.

In this study, we have explored the prevention of gastric side effects such as gastric lesions and bleeding while maintaining the high analgesic and anti-inflammatory activities by the derivatization of the carboxylate moiety into amides in [5-chloro-6-(2-chloro/fluorobenzoyl)-2-benzoxazolinone-3-yl]acetic acids. We have tested the analgesic and anti-inflammatory activities of the synthesized compounds in vivo by using p-benzoquinone-induced writhing test and carrageenan-induced hind paw edema model, respectively. Compounds 3a, 3d, 3e, 3j and 3k potent analgesic and anti-inflammatory activities without gastric lesions in the tested animals. Therefore, conversion of the carboxylate moiety into certain amide derivatives generated potent analgesic and anti-inflammatory compounds while eliminating the gastrointestinal side effects. Cyclooxygenase (COX)-selectivity of the active compounds was also investigated by using in vitro human whole blood assay. Compounds 3a, 3e, 3h and 3k selective inhibition of COX-2 to some extent although the inhibitory activity was not very potent.