An Effective Approach to the Disinfection of Pathogens: Cationic Conjugated Polyelectrolytes and Oligomers.

The synthetic cationic conjugated polyelectrolytes and oligomers have demonstrated great effectiveness and versatility as antimicrobial materials. They have the ability to eliminate or render inactive various pathogens, including viruses like SARS-CoV-2, bacteria, and fungi. These pathogens can be rapidly eradicated when the polyelectrolytes and oligomers are applied as sprays, wipes, or coatings on solid surfaces. Inactivation of the pathogens occurs through two distinct processes: a non-light-activated process similar to Quats, and a more efficient and faster process that is triggered by light. These materials possess fluorescence and photosensitizing properties, enabling prolonged protection when coated on surfaces. The level of fluorescence exhibited by samples applied to nonfluorescent surfaces serves as an indicator of the coating's integrity and viability, making it easily detectable. Importantly, these materials demonstrate low toxicity towards mammalian cells and human skin, allowing for their safe use. While they can serve as durable coatings for pathogen protection, extended exposure to visible or ultraviolet light leads to their photochemical degradation. Our research also suggests that these materials act against pathogens through nonspecific mechanisms, minimizing the likelihood of pathogens developing resistance and rendering the materials ineffective.

SuFExable NH-Pyrazoles via 1,3-Dipolar Cycloadditions of Diazo Compounds with Bromoethenylsulfonyl Fluoride.

"Click" reactions have transformed the molecular sciences. Augmenting cycloaddition reactions, sulfur(VI) fluoride exchange (SuFEx) chemistry has diversified the landscape of molecular assembly. Herein, we report a facile strategy to access SuFExable NH-pyrazoles via strain and catalyst-free 1,3-dipolar cycloadditions of stabilized diazo compounds under mild conditions. Subsequent SuFEx proceeds efficiently with various N- and O-nucleophiles. Access to SuFExable NH-pyrazoles─a class of compounds containing two common pharmacophores─enables future opportunities within drug discovery, chemical biology, materials chemistry, and related fields.

Rapid and Effective Inactivation of SARS-CoV-2 with a Cationic Conjugated Oligomer with Visible Light: Studies of Antiviral Activity in Solutions and on Supports.

This paper presents results of a study of a new cationic oligomer that contains end groups and a chromophore affording inactivation of SARS-CoV-2 by visible light irradiation in solution or as a solid coating on paper wipes and glass fiber filtration substrates. A key finding of this study is that the cationic oligomer with a central thiophene ring and imidazolium charged groups gives outstanding performance in both the killing of E. coli bacterial cells and inactivation of the virus at very short times. Our introduction of cationic N-methyl imidazolium groups enhances the light activation process for both E. coli and SARS-CoV-2 but dampens the killing of the bacteria and eliminates the inactivation of the virus in the dark. For the studies with this oligomer in solution at a concentration of 1 µg/mL and E. coli, we obtain 3 log killing of the bacteria with 10 min of irradiation with LuzChem cool white lights (mimicking indoor illumination). With the oligomer in solution at a concentration of 10 µg/mL, we observe 4 log inactivation (99.99%) in 5 min of irradiation and total inactivation after 10 min. The oligomer is quite active against E. coli on oligomer-coated paper wipes and glass fiber filter supports. The SARS-CoV-2 is also inactivated by oligomer-coated glass fiber filter papers. This study indicates that these oligomer-coated materials may be very useful as wipes and filtration materials.

Optimizing Protonation States for Selective Double-Strand DNA Photocleavage in Hypoxic Tumors: pH-Gated Transitions of Lysine Dipeptides.

We report pH-switching properties of the new family of dipeptide-acetylene conjugates where pH-gated light-activated double-strand (ds) DNA cleavage is controlled by variations in electronic and geometric parameters. The conjugates have higher activities at the slightly acidic pH values that separate normal and cancerous tissue (pH < 7). This favorable pH dependence originates from several elements of structural design. Basicities of the two amines determine the threshold pH range where the changes in binding and reactivity are observed, whereas the distance between the two amino groups and the hydrophobic aryl alkyne moiety can further modulate DNA binding. The changes of the protonation state from a neutral molecule to a dication results in dramatically increased efficiency of ds DNA photocleavage, the most therapeutically valuable type of DNA cleavage.

Opening Enediyne Scissors Wider: pH-Dependent DNA Photocleavage by meta-Diyne Lysine Conjugates.

Photochemical activation of meta-diynes incapable of Bergman and C1-C5 cyclizations still leads to efficient double-strand DNA cleavage. Spatial proximity of the two arylethynyl groups is not required for efficient DNA photocleavage by the enediyne-lysine conjugates. Efficiency of the cleavage is a function of the external pH and DNA damage is strongly enhanced at pH < 7. The pH-dependence of the DNA photocleavage activity stems from the protonation states of lysine amino groups, the internal electron donors responsible for intramolecular PET quenching and deactivation of the photoreactive excited states. DNA-binding analysis suggests intercalative DNA binding for phenyl substituted conjugate and groove binding for TFP-substituted conjugate. Additional insights in the possible mechanism for DNA damage from the ROS (Reactive Oxygen Species) scavenger experiments found that generation of singlet oxygen is partially involved in the DNA damage.

Association between suicidal ideation and behavior, and depression, anxiety, and perceived social support in cancer patients.

BACKGROUND: The aim of this study was to determine the relationship between suicidal behavior and associated factors such as depression, anxiety, and perceived social support level in cancer patients. MATERIAL AND METHODS: The study group included 102 patients who were under treatment in the oncology department and the control group included 100 individuals with similar sociodemographic features. A sociodemographic information form, Beck depression inventory, Beck anxiety inventory, suicidal behavior inventory, suicidal ideation inventory, and multidimensional inventory of perceived social support were used. RESULTS: The mean Beck depression inventory and Beck anxiety inventory scores in the study group were significantly higher compared to the control group. Thirteen patients in the study group attempted suicide, whereas 3 individuals attempted suicide in the control group. Similarly, the mean suicide behavior and ideation scores in the study group were significantly higher compared to the control group. The mean total multidimensional inventories of perceived social support score, as well as the mean family and friend sub-inventory scores in the control group were significantly higher compared to the study group. CONCLUSIONS: This study revealed that depression and anxiety occur frequently in cancer patients. Suicide attempts and ideation are higher in cancer patients compared to the control group. Social support perceived from family and friends is lower in cancer patients. Suicide attempts are correlated with depression, anxiety, low level of perceived social support, and advanced disease stage.

Pulmonary thromboembolism due to paliperidone: report of 2 cases.

Venous thromboembolism (VTE) is serious medical condition, which might be caused by psychotropic medications. Previously, antipsychotic-induced VTE due to olanzapine, risperidone, clozapine, and amisulpiride was reported. In this report, we present 2 cases of paliperidone-induced VTE.

Hybrids of amino acids and acetylenic DNA-photocleavers: optimising efficiency and selectivity for cancer phototherapy.

Hybrid agents which combine potent DNA-photocleavers with tunable amino acids or small peptides were designed to improve selectivity of Nature's most potent class of antibiotics towards cancer cells. The ability of these compounds to photocleave DNA is controlled by their incorporation into hybrid architectures with functional elements derived from natural amino acids. These conjugates are highly effective at inducing double-strand DNA cleavage and, in some cases, rival or even surpass both naturally occurring DNA cleavers and anticancer agents that are currently in clinical use. The possibility of triggering their activity in a photochemical and pH-sensitive fashion allows for a high degree of selectivity over activation. The conjugates were shown to penetrate cell membranes and induce efficient intracellular DNA cleavage. Initial in vitro tests against a variety of cancer cell lines confirm the potential of these compounds as anticancer agents at low nanomolar concentrations.

Effect of hypothyroidism on the nitrergic relaxant responses of corpus cavernosal smooth muscle in rabbits.

BACKGROUND: The incidence of hormonal dysfunction as a cause of impotence remains controversial. However, several recent studies have reported evidence of hormonal abnormalities in 25-35% of impotent men. Hypothyroidism has been reported to occur in 6% of impotent men. METHODS: In the present study, we examined nitrergic responses in hypothyroidism in rabbit corpus cavernosum and compared them with controls. RESULTS: Carbachol-induced relaxation responses and electrical field stimulation (EFS)-induced frequency-dependent relaxations decreased significantly in hypothyroid rabbits. Papaverine and sodium nitroprusside (SNP)-induced relaxation responses did not change significantly in hypothyroid rabbits. The contraction responses of phenylephrine and EFS-induced frequency-dependent contractions were significantly decreased in the hypothyroid group. CONCLUSIONS: We can speculate that the reduction of relaxant responses to EFS and carbachol in hypothyroid rabbits can depend on a decreased release of nitric oxide (NO) from nitrergic nerves and endothelium or a reduction of muscarinic receptor density. Also, decreases in contraction responses may depend on diminished adrenoceptor density.

Efficacy of tolterodine as a first-line treatment for non-neurogenic voiding dysfunction in children.

OBJECTIVE: To assess the effect of antimuscarinic treatment with tolterodine combined with behavioural modification as a first-line treatment, before invasive investigation, in children with non-neurogenic voiding dysfunction but no obvious anatomical or neurogenic cause. PATIENTS AND METHODS: The study comprised 44 children presenting with voiding dysfunction (30 girls and 14 boys, mean age 7 years, range 5-14); all had a noninvasive evaluation consisting of a history, urine analysis, renal and bladder ultrasonography and physical examination, with specific emphasis on the voiding pattern. Anticholinergic treatment with tolterodine (1 mg twice daily) was started in all patients; they were also informed about conservative management, including timed voiding, double voiding and relaxation of the pelvic floor during voiding. At the start and after 3 months, the dysfunctional voiding symptom score (DVSS) was completed twice by all patients. RESULTS: For all patients the mean (sd) DVSS was 14.0 (2.67) and 6.68 (3.67) before and after treatment, respectively; the difference was statistically significant (P < 0.001). The mean scores for girls and boys, respectively, were 13.8 (2.79) and 14.5 (2.44) before and 6.43 (3.79) and 7.50 (3.34) after treatment. CONCLUSION: Tolterodine combined with behavioural modification for dysfunctional voiding in children with no neurological or anatomical abnormality can be recommended as a first-line treatment before invasive evaluation. Additionally, the DVSS appears to provide accurate and objective data for monitoring the effect of treatment in such children.

Epidermoid cyst in the renal pelvis.

Epidermoid cysts are benign cysts localizing rarely in solid organs with an unclear pathogenesis. A 55 years old woman having an epidermoid cyst in the renal pelvis was evaluated according to the literature.

Role of genital mycoplasmata and other bacteria in urolithiasis.

Urease-producing bacteria have been shown to affect the formation of infection stones by splitting urea into ammonia, bicarbonate and carbonate. An increase in alkaline pH results in urinary supersaturation of the ions. The increase in ammonia also causes injury to the urothelial glycosaminoglycan layer. Non-urease-producing bacteria have been speculated to form urinary stones. Midstream voided bladder urine and fractured stone nidus samples from 72 patients undergoing surgery for urolithiasis were cultured on specific media for genital mycoplasmata and on conventional media. Urine samples were obtained from a control group of 40 healthy subjects. Genital mycoplasmata and other bacteria were evaluated with regard to the composition of urinary stones. Compared with other origins of stones, the relation between isolation of Ureaplasma urealyticum and infection stone disease was statistically proven. Isolation of genital mycoplasmata was significantly higher in women than in men in the study group. The urinary stones comprised 84.7% calcium stones, 8.3% uric acid stones and 6.9% infection (magnesium ammonium phosphate) stones. Coagulase-negative Staphylococci, Escherichia coli, Corynebacterium spp., Enterobacterium spp. and U. urealyticum were cultured from stone samples. The results suggests that non-urease-producing bacteria, as well as urease-producing bacteria, may influence the formation of urinary stones.

[Surgical treatment of penil fractures]. / Penis fraktürlerinin cerrahi tedavisi.

BACKGROUND: Patients diagnosis as penil fracture and treated with surgical methods were evaluated retrospectively between January 1990-February 2002. METHODS: Patients were evaluated by age, trauma type, time passed after the trauma, physical examination and radiologic data. RESULTS: The cause of trauma was blunt trauma in all patients. 14 trauma (60.8%) were during sexual activity, 6 trauma (26%) were during handling the erective penis in morning erection, 3 of trauma (13%) were due to the rolling on to the penis. Urethral bleeding was seen in 1 patient and microscopic hematuria was detected in 5 patients. Subcoronal circular incision was carried out in 16 patients (69.5%), semicircular incision was done directly on the injury in 6 patients (26%) and from penis radix to scrotum was done in 1 patient (4.3%). There was unilateral corpus cavernosum injury in 21 patients. Bilateral corpus cavernosum injury in 1 patient, corpuscavernosum, corpus spongiosum and incomplent urethral injury in 1 patient. Wound infection was detected only in 2 patients at postoperatively early period. After evaluating 20 patients with medical history and physical examination in postoperative control penil curvature permitting sexual activity was detected in 3 patients. CONCLUSION: We concluded that patients with penil fracture may be treated with low complication rate by early surgical procedure.

Genitourinary tuberculosis: a review of 174 cases.

In 174 cases of genitourinary tuberculosis diagnosed and treated in our clinic we evaluated, retrospectively, age and sex distributions, symptoms, physical and laboratory findings, primary focus, surgical and medical treatments. Flank pain and non-specific urinary complaints, e.g. dysuria, were the major symptoms. Although some authors prefer short-term medical therapy for the treatment of genitourinary tuberculosis, the relapse rate in our series after 12 months of therapy was 19% and we therefore suggest that therapy should be continued for at least 12 months. The poor nutritional status and social conditions characteristic of subjects from our region may, however, have influenced this high relapse rate.