Primary Mono Research Articles

Bed Wetter: An Upset 9 Y Old Boy with Primary Mono symptomatic Nocturnal Enuresis

Background: Bed wetting or nocturnal enuresis is seen in 15% of children over 5 Yr. it is primary in 75-90% of cases and the monosymptomatic enuresis is more common and should be estimated after ruling out other symptoms. In here we report a case of a 9-year-old boy who referred with a permanent primary monosymptomatic nocturnal enuresis and he was quite upset and had a tired and unhappy family. Case Presentation: This is a clinical combined therapy case study. A 9-year-old boy was referred with a chief complaint of bed wetting, which was primary and monosymptomatic, but because of experiencing of wrong incomplete period of treatments, they were disappointed. He had tried one or two drugs each time. In this approach I put him under simultaneous given multifaceted treatment, include education and advises, motivational therapies, conditional therapy, and pharmacotherapies. And this situation revealed a faster and also more persistent result and this motivated the child and his family to complete the treatment course (for 4 months) without any relapse after completion this period. Conclusion: Our study shows that nocturnal enuresis, even primary monosymptomatic types, which are most common types of enuresis may need multi-faceted treatment to make child calm and his family comfort.

Hybrid grafted and hyperbranched anion exchangers for ion chromatography

Novel grafted anion exchangers with covalently bonded hyperbranched functional layers were prepared and evaluated for the separation of monovalent standard inorganic anions and oxyhalides. Preparation of base coating included grafting highly polar N-vinylformamide to the ethylvinylbenzene-divinylbenzene (EVB-DVB) substrate surface in highly polar solvent (methanol) with subsequent hydrolysis of grafted amide polymer in basic media, which resulted in preparation of polymer chains with multiple primary amino groups. Those amino groups were used as attachment points for forming hyperbranched anion-exchange layers using 1,4-butanediol diglycidyl ether and primary mono- or diamine (methylamine or 1,3-diaminopropane, respectively). The effects of hyperbranching reaction cycles number on selectivity were evaluated which revealed that selectivity and capacity can be controlled independently for the covalently bonded stationary phases in contrast to electrostatically bonded phases. It was demonstrated that unlike for electrostatically bonded phases, the intentional increase of crosslink by using primary diamine instead of primary monoamine doesn't cause the shift of selectivity coefficients. It was also shown that crosslink distribution throughout the hyperbranched layer is an important factor determining selectivity of hyperbranched anion exchangers.

Comparative Analysis of Solifenacin Plus Desmopressin Versus Desmopressin Alone in the Treatment of Primary Mono Symptomatic Nocturnal Enuresis

ObjectivesTo compare the efficacy and tolerability of Solifenacin plus Desmopressin and Desmopressin alone in the treatment of primary monosymptomatic nocturnal enuresis (PMNE). MethodsA total of 88 children, 5–14 years old, diagnosed with PMNE were enrolled in this randomized control trial (RCT) from June 2017 to June 2020. After informed written consent patients were randomized to one of the two therapeutic groups. Group 1 received one puff of desmopressin nasal spray 1 h before bedtime every night. Group 2 received one pill of solifenacin 5 mg plus one puff of desmopressin nasal spray 1 h before bedtime every night. All patients were evaluated after three months for their response to treatment and drug side effects. ResultsThe mean age in desmopressin alone group and solifenacin plus desmopressin group was 8.1 ± 2.2 (5–14) and 7.9 ± 2.2 (5–14) years respectively (p-value >0.05). In group 2, 37/44 (84.09%) patients achieved complete response after three months of treatment in comparison to group 1 in which 27/44 (61.36%) patients showed complete response (p-value <0.05). In group 1, 8/44 (18.18%) patients developed treatment related side effects whereas in group 2, 12/44 (27.27%) patients developed side effects (p-value >0.05). No case of discontinuation of treatment due to side effects was observed in any of the two groups. The recurrence rate was also significantly lower in group 2 in comparison to group 1 (8.1% vs 33.3%, p-value <0.05). ConclusionOur study demonstrated that the combination of Solifenacin plus Desmopressin is more effective than desmopressin monotherapy in the treatment of PMNE with an acceptable tolerability profile. Level of EvidenceLevel I.

Coconut oil rubbing as an easy and safe way to improve symptoms in primary nocturnal enuresis: A randomized double-blinded placebo-controlled clinical trial.

Objective:Enuresis is a common pediatric problem for which, no unique therapy has been suggested. The conventional therapy is effective, but fails in some cases. So, many parents try complementary medicine. Therefore, this study attempted to find if rubbing coconut oil is effective on improving enuresis.Materials and Methods:This double-blinded randomized clinical was conducted on 120 children aged 6 to 14 years with mono symptomatic nocturnal enuresis, from 2018 to 2019 in Yazd, Iran. The drug and placebo groups applied 6 drops of the coconut and paraffin oil topically on the suprapubic, sacral and flanks areas one time per night, respectively. Urination pattern was daily recorded for a period of 8 weeks by parents, and after one year, they were asked for any improvement by phone call.Results:The mean frequency of enuresis at the first, second, fourth, and eighth week was lower in the intervention group (p<0.001); this difference between the groups remained after one year. Moreover, there was no side effect requiring any medical attention.Conclusion:Rubbing coconut oil is effective on improving symptom of primary mono symptomatic enuresis if applied every night for 4 weeks on suprapubic, sacral and flanks areas. This may be related to anticholinergic effect of the oil but its persistent effect for longer time after the end of application period, needs to be investigated in other studies.

Insights into mechanisms involved in the uptake, translocation, and metabolism of phthalate esters in Chinese cabbage (Brassica rapa var. chinensis)

In the present study, the uptake and translocation mechanisms of phthalate esters (PAEs) and their primary mono esters metabolites (mPAEs), and the mechanisms of PAEs metabolism in plants were elucidated. The objectives of this study were to: (i) elucidate the fractionation of PAEs and mPAEs in Chinese cabbage (Brassica rapa var. chinensis) by hydroponic experiment, (ii) investigate the PAEs and mPAEs uptake mechanisms in root by inhibitor experiments, (iii) explain the molecular mechanisms of PAE interactions with the plant macromolecules by proteomics analysis and molecular docking, and (iv) reveal the involvement of carboxylesterase in the plant metabolism of PAEs. The results demonstrated that both the apoplastic and symplastic pathways contributed to the uptake of di-n-butyl phthalate (DnBP), di-(2-ethylhexyl) phthalate (DEHP), mono-n-butyl phthalate (MnBP), and mono-(2-ethylhexyl) phthalate (MEHP) by vacuum-infiltration-centrifugation method. The energy-dependent active process was involved for the uptake of DnBP, DEHP, MnBP, and MEHP. The passive uptake pathways of anion mPAEs and neutral PAEs differ. Aquaporins contributed to the uptake of anion MnBP and MEHP, and slow-type anion channel was also responsible for the uptake of anion MEHP. Molecular interactions of PAEs and macromolecules were further characterized by proteomic analysis and molecular docking. PAEs were transferred via non-specific lipid transfer protein by binding hydroponic amino acid residues. The carboxylesterase enzyme was attributed to the metabolism of PAEs to form mPAEs by using crude enzyme extract and commercial pure enzyme. This study provides both experimental and theoretical evidence for uptake, accumulation, and metabolism of PAEs in plants.

Synthesis of novel polycarbonyl Schiff bases by ring-opening reaction of ethyl 5-acyl-4-pyrone-2-carboxylates with primary mono- and diamines.

An approach for the introduction of the tricarbonyl moiety into aromatic, heterocyclic, and aliphatic amines with the use of acylpyrones has been developed for the synthesis and the design of novel polycarbonyl Schiff base ligands, including salphen structures. This Michael addition–ring-opening reaction proceeds under mild conditions (stirring at 0–20 °C) via the attack at the C-6 position of the pyrone ring in good to high yields (up to 99%) with excellent selectivity. The products can be easily isolated by crystallization without the use of chromatography. The scope of the reaction, tautomeric equilibrium of open-chain products, and their cyclization into pyridone structures were investigated.

Human carbonic anhydrase inhibitory profile of mono- and bis-sulfonamides synthesized via a direct sulfochlorination of 3- and 4-(hetero)arylisoxazol-5-amine scaffolds

Three distinct series of isoxazole-based primary mono- and bis-sulfonamides have been synthesized via direct sulfochlorination, each of them delivering nanomolar inhibitors of human carbonic anhydrase. Certain pronounced SAR trends have been established and rationalized by in silico docking. These findings expand the structure-activity knowledge base for heterocycle-containing sulfonamide carbonic anhydrase inhibitors and further validate the power of direct electrophilic sulfochlorination as a means of introducing the pharmacophoric primary sulfonamide group into structurally diverse aromatic precursors.

Primary mono- and bis-sulfonamides obtained via regiospecific sulfochlorination of N-arylpyrazoles: inhibition profile against a panel of human carbonic anhydrases

A diverse set of mono- and bis-sulfonamide was obtained via a direct, chemoselective sulfochlorination of readily available yet hitherto unexplored N-arylpyrazole template. Biochemical profiling of compounds thus obtained against a panel of human carbonic anhydrases (hCA I, hCA II, hCA IV and hCA VII) revealed a number of leads that are promising from the isoform selectivity prospective and exhibit potent inhibition profile (from nanomolar to micromolar range). The observed SAR trends have been rationalized by in silico docking of selected compounds into the active site of all four isoforms. The results reported in this paper clearly attest to the power of direct sulfochlorination as the means to create carbonic anhydrase focused sets in order to identify isoform selective inhibitors of closely related enzymes.

A prospective longitudinal study to estimate the prevalence of obesity in Egyptian children with nocturnal enuresis and the association between body mass index and response to therapy

PurposeNocturnal enuresis is defined as the involuntary voiding of urine in bed beyond the age at which bladder control is normally obtained. Previous studies have suggested a high rate of obesity in children with nocturnal enuresis. We evaluated this hypothesis and investigated the correlation between body mass index and the efficacy of treatment. Subjects and methodsThis was a prospective–longitudinal study done on 180 children with primary mono symptomatic nocturnal enuresis. Urinary diary data and body mass index percentile were determined. Response to the treatment was evaluated statistically and correlated with body mass index percentile. Response to different modalities of the treatment were also statistically evaluated separately and correlated with the BMI. The statistical test used was ANOVA F-test. Results22.7% of our patients with nocturnal enuresis were either overweight or obese (13.9% and 7.8% respectively) according to the Egyptian national growth charts. Therefore, the prevalence of overweight and obesity is not higher in children with nocturnal enuresis as compared to the overall prevalence in normal Egyptian children (14%). But when we adjusted these values according to the social class of our patients, the prevalence of obesity was higher than normal for children of low socioeconomic status.There was no significant correlation between response to standard pediatric urological interventions (behavioral therapy, alarm therapy, imipramine, desmopressin, oxybutynin and tolterodine) and the BMI of our patients. Also, there was no significant difference in the response or relapse rates to the different modalities of therapies in the groups of patients with different BMI. ConclusionsObesity correlates with high BMI in lower socioeconomic classes, but does not correlate with efficacy of the treatment in children with nocturnal enuresis.

Assessment of the Most Frequently Used Modalities of Treatment for Primary Mono Symptomatic Nocturnal Enuresis in Egypt

Assessment of the Most Frequently Used Modalities of Treatment for Primary Mono Symptomatic Nocturnal Enuresis in Egypt

P. gingivalis Modulates Keratinocytes through FOXO Transcription Factors

P. gingivalis is a prominent periodontal pathogen that has potent effects on host cells. In this study we challenged gingival epithelial cells with P. gingivalis with the aim of assessing how mRNA levels of key target genes were modulated by P. gingivalis via the transcription factors FOXO1 and FOXO3. Primary mono- and multi-layer cultures of gingival epithelial cells were challenged and barrier function was examined by fluorescent dextran and apoptosis was measured by cytoplasmic histone associated DNA. Gene expression levels were measured by real-time PCR with and without FOXO1 and FOXO3 siRNA compared to scrambled siRNA. P. gingivalis induced a loss of barrier function and stimulated gingival epithelial cell apoptosis in multilayer cultures that was in part gingipain dependent. P. gingivalis stimulated an increase in FOXO1 and FOXO3 mRNA, enhanced mRNA levels of genes associated with differentiated keratinocyte function (keratin-1, -10, -14, and involucrin), increased mRNA levels of apoptotic genes (BID and TRADD), reduced mRNA levels of genes that regulate inflammation (TLR-2 and -4) and reduced those associated with barrier function (integrin beta-1, -3 and -6). The ability of P. gingivalis to modulate these genes was predominantly FOXO1 and FOXO3 dependent. The results indicate that P. gingivalis has pronounced effects on gingival keratinocytes and modulates mRNA levels of genes that affect host response, differentiation, apoptosis and barrier function. Moreover, this modulation is dependent upon the transcription factors FOXO1 or FOXO3. In addition, a new function for FOXO1 was identified, that of suppressing TLR-2 and TLR-4 and maintaining integrin beta -1, beta -3 and beta -6 basal mRNA levels in keratinocytes.

A Highly Efficient Synthesis of Optically Active Ferrocenylethylamines via Hydride Reduction of Chiral Ferrocenylketimines

AbstractDue to using (R)‐ or (S)‐α‐methylbenzylamine as a chiral auxiliary, and low‐temperature regime for reduction of the intermediate ferrocenyl‐mono‐ or 1,1′‐bis‐ketimines, the corresponding secondary mono‐ or 1,1′‐bis‐amines were prepared with high diastereoselectivity. Removal of the α‐methylbenzyl group afforded the optically active primary mono‐ and bis‐ferrocenylethylamines in high yields. The absolute configuration of (R,R)‐3a and (S,S)‐3b was determined by X‐ray single crystal diffraction.

3‐Azidopropylamine is an excellent substrate of lysyl oxidase

Lysyl oxidase (LOX) is a copper‐containing amino oxidase which physiological function is oxidative deamination of lysine side chains in collagen, elastin etc for subsequent formation of protein‐protein cross‐links. Substrate specificity of LOX was characterized in numerous studies and it is well known that LOX can utilize various primary mono‐ and diamines such hexylamine or 1,5‐diaminopentane. Here we report that introduction of an azide group can greatly affect substrate properties. 3‐Azidopropylamine has been synthesized from bromopropylamine and purified by distillation. Both LOX prepared from sheep aorta and recombinant mouse LOX overexpressed in E. coli showed highly efficient oxidation of 3‐azidopropylamine measured as release of hydrogen peroxide. Kinetics is complex with substrate inhibition at high concentrations: apparent Ki 2.5 mM and apparent Ks 13 μM, the latter being much better than that for any other known low molecular weight substrate. Hypothetically, azidoalkylamines have these remarkable properties due to interaction of the azide group with LOX‐bound copper. Interestingly, 3‐azidopropylamine has no overt cell toxicity below millimolar concentrations and, therefore, may be used for in vivo studies. Supported by MCB Program of the Presidium of Russian Academy of Sciences.

PREVALENCE OF DIURNAL VOIDING SYMPTOMS AND DIFFICULT AROUSAL FROM SLEEP IN CHILDREN WITH NOCTURNAL ENURESIS

We analyzed the relative contribution of detrusor instability and difficult arousal from sleep in the genesis of nocturnal enuresis (NE), and evaluate a clinical feature that may prospectively help differentiate patients with monosymptomatic NE (mono NE) from those with diurnal voiding symptoms (DVSs) of urgency and urge incontinence associated with NE (NE + DVSs). Patients referred for voiding problems and 627 controls were evaluated for NE, DVSs, nocturia and arousal from sleep on a scale of 1 to 8. Patients were categorized into 3 groups-mono NE of primary or secondary onset (200, boys 71%, girls 29%), primary or secondary NE + DVSs (329, boys 43%, girls 57%) and isolated DVSs (146, boys 21%, girls 79%). DVSs were noted in 49% of boys and 76% of girls with NE, although 40% of patients or parents did not complain of DVSs. The DVSs were elicited on detailed interrogation or on finding evidence of urinary incontinence on perineal examination. While one-third of controls and patients with isolated DVSs manifested nocturia at least twice a month, only 6% of bedwetters did so. Difficult arousal from sleep (scores 6 to 8) was more prevalent in patients with NE (59%) than controls (20%) or patients with isolated DVSs (5%), and in patients with mono NE and primary NE than in NE + DVSs or secondary NE, with reverse prevalence for nocturia. Easy sleep arousal (scores 1 to 3) was noted in 65% of patients with secondary NE + DVSs vs up to 6% of other NE subgroups. Compared to patients with mono NE, those with NE + DVSs had a higher prevalence of urinary tract infection (UTI), encopresis, psychosocial/learning problems, and family history of UTI and DVSs, ie problems associated with detrusor instability. DVSs accompany NE in two-thirds of patients but can be missed during a cursory history. Difficult sleep arousal seems to have a major role in primary mono NE, and detrusor instability in secondary NE + DVSs. In patients with NE a history of frequent nocturia, easy sleep arousal, UTI, encopresis, psychosocial learning problems or family history of UTI and DVSs should raise the suspicion for associated undisclosed DVSs.

Poly(amido-amine)s: Biomedical Applications

Poly(amido-amine)s (PAAs) are synthetic tert-amino polymers obtained by stepwise polyaddition of primary or secondary aliphatic amines to bis(acrylamide)s. Linear polymers are produced during the polymerisation of both primary mono(amine)s and secondary bis(amine)s. Under non-selective conditions primary bis(amine)s usually give crosslinked products upon reaction with bis(acrylamide)s, i. e., they react as tetrafunctional monomers. Furthermore, end-functionalised PAAs can be used to prepare block or graft copolymers, as well as crosslinked resins. PAAs can therefore be regarded as macromonomers as well. Generally, PAAs are soluble in water, chloroform, lower alcohols, dimethyl sulfoxide and other polar solvents (although amphoteric PAAs can only be dissolved in water). PAAs are degradable in aqueous solution by means of hydrolytic cleavage of the amidic bonds in their main chain that are activated by the tert-amino groups present in ?-position. A vast library of PAA structures has now been reported that are suitable for numerous material and biomedical applications. Here we review the synthesis, characterisation and current biomedical uses of PAAs. Their use as heavy-metal-ion-complexing polymers, and polymers for heparin neutralisation in solution, fabrication of heparin-absorbing resins and heparinisable materials is discussed. As amphoteric PAAs are biocompatible and biodegradable polymers that moreover display intelligent stealth properties, they are currently under development as PAA/anticancer conjugates and non-viral vectors for intracytoplasmic delivery. The potential of this unique chemistry is reviewed.

Transition Metal Complexes of Organothiophosphorus Ligands. IX. Adducts of Nickel Alkoxy- and Phenoxyethyl Phosphorodithioates with Primary and Tertiary Mono- and Diamines

Abstract Primary mono- and diamines (p-toluidine, 1,2-ethylene-diamine, o- and p-phenylenediamine, 4,4′-diaminodiphenyl) and tertiary aromatic mono and diamines (pyridine, 3- and 4-picoline, o-phenanthroline and 4,4′-bipyridyl) form amine adducts with Ni(R-L)2 [Me-L=(CH3OCH2CH20)2PS2 −; Et-L=(C2H5OCH2CH2O)2PS2 −; Ph-L=(C6H5OCH2CH2O)2PS2 −]. Possible structures are suggested on the basis of electronic and infrared spectra.

Structure–reactivity relationships and the rate–determining step in the reactions of methyl salicylate with primary amines

AbstractThe aqueous cleavage of methyl salicylate has been studied in the buffer solutions of various primary mono‐ and di‐amines as well as secondary amines at 30°C. Both ionized (MS−) and nonionized (MSH) methyl salicylate are reactive toward primary mono‐ and di‐amines. The second‐order rate constants for the reactions of MS− with primary mono‐ and di‐amines of pKa &gt; 9.4 exhibit Bronsted plot of slope (βnuc) of 0.82. This high value of βnuc is attributed to an intramolecular proton transfer in a thermodynamically unfavorable direction in the rate‐determining step in a stepwise process for the formation of monoanionic tetrahedral intermediate. However, a concerted process for the formation of a monoanionic tetrahedral intermediate in the reactions of MS− with amine nucleophiles wherein expulsion of leaving group is a rate‐determining step is not completely ruled out. The α‐effect nitrogen nucleophiles hydroxylamine and hydrazine reveal, respectively, ca. 104‐ and 103‐fold higher reactivity compared to other amine nucleophiles of comparable basicity. The value of βnuc of 1.03 obtained for the reactions of primary monoamines with MSH is ascribed to the expulsion of leaving group as the rate‐determining step. The significantly lower value of βnuc of 0.60 obtained in the reactions of MSH with both monoprotonated and unprotonated diamines is explained in terms of possible occurrence of intramolecular general acid‐base catalysis. Intramolecular general base catalysis is responsible for the enhanced nucleophilic reactivity of primary amines toward MS−. Dimethylamine, piperidine, morpholine, and piperazine have no detectable nucleophilic reactivity toward MS−.

Catalyse chimique par le systeme nickel-2,2′-bipyridine de la reduction electrochimique d'halogenures aliphatiques

In dimethylformamide or N-methylpyrrolidone the Ni-bipyridyl system catalyses the electrochemical reduction of functionalised or non-functionalised aliphatic halides. High yields of dimeric products are obtained besides primary mono- or di-bromides. Analysis of the reaction products shows the formation of dialkylnickel which can be isolated by coulometry. This species acts as a reducing agent for aliphatic halides.

Effect of pentobarbital on neuronal inhibitory response evoked in an isolated slab of cat auditory cortex by intracortical stimulation

Neuronal responses of an acutely isolated slab of auditory cortex (area AI) to intracortical electrical stimulation were studied intracellularly in cats anesthetized with pentobarbital. It was found that 77% of responses were primary IPSPs, and allowing for secondary inhibitory responses, an inhibitory response was observed in 92% of neurons. All types of neuronal responses in the slab were short-latency. The maximal response latency did not exceed 5 msec. Neurons responding to stimulation by IPSPs were found at all depths in the slab, with a maximum in layers II–III. Nearly all primary IPSPswere mono- and disynaptic. Pentobarbital increased the duration of individual neuronal inhibitory responses in the isolated slab of auditory cortex without affecting maximal duration of the IPSP. The mechanisms of the effect of pentobarbital on the amplitude and duration of IPSPs are discussed.

A simple method for the separation of primary mono- and diamines using a standard amino acid analyzer

A simple method for the separation of primary mono- and diamines using a standard amino acid analyzer