Semi-Synthetic Dihydrotestosterone Derivatives Modulate Inherent Multidrug Resistance and Sensitize Colon Cancer Cells to Chemotherapy.

Multidrug resistance (MDR) is a serious hurdle to successful cancer therapy. Here, we examined the efficiency of novel semi-synthetic dihydrotestosterone derivatives, more specifically androstano-arylpyrimidines in inhibiting the efflux activity of ATP-binding cassette (ABC) transporters and sensitizing inherently MDR colon cancer cells to various chemotherapy drugs. Using the Rhodamine123 accumulation assay, we evaluated the efflux activity of cancer cells following treatments with androstano-arylpyrimidines. We found that acetylated compounds were capable of attenuating the membrane efflux of inherently MDR cells; however, deacetylated counterparts were ineffective. To delineate the possible molecular mechanisms underlying these unique activities of androstano-arylpyrimidines, the degree of apoptosis induction was assessed by AnnexinV-based assays, both upon the individual as well as by steroid and chemotherapy agent combination treatments. Five dihydrotestosterone derivatives applied in combination with Doxorubicin or Epirubicin triggered massive apoptosis in MDR cells, and these combinations were more efficient than chemotherapy drugs together with Verapamil. Furthermore, our results revealed that androstano-arylpyrimidines induced significant endoplasmic reticulum stress (ER stress) but did not notably modulate ABC transporter expression. Therefore, ER stress triggered by acetylated androstano-arylpyrimidines is probably involved in the mechanism of efflux pump inhibition and drug sensitization which can be targeted in future drug developments to defeat inherently multidrug-resistant cancer.

Peritonsillar abscess: an 8-year retrospective, culture based evaluation of 208 cases.

Introduction. Peritonsillar abscess (PTA) is a common infection which requires surgical intervention and suitable antibiotic therapy.Hypotheses/Gap Statement. Beside Streptococcus pyogenes and Fusobacterium necrophorum several other mostly anaerobic bacteria can be cultured from the properly taken pus samples of PTA, the clinical significance of which is still not fully understood.Aim. This study focused on the culture-based microbiological evaluation of PTA cases, compared to surgical intervention and empirical antibiotic management.Methodology. A retrospective analysis of PTA cases was performed between 2012 and 2019. Data about the aerobic and anaerobic culture results of the samples taken during different surgical interventions were summarized and the coverage of the empirically selected antibiotics was evaluated. The patient's history, the development of complications and the recurrence rate were also evaluated.Results. The microbiological culture results were available for 208 of 320 patients with clinically diagnosed PTA. Incision and drainage (I and D) and immediate tonsillectomy were the leading surgical interventions. Ninety-five Fusobacterium species (including 44 Fusobacterium necrophorum), 52 Actinomyces species and 47 Streptococcus pyogenes were obtained from PTA samples alone or together with polymicrobial flora. S. pyogenes (33.7 %, n=28) and F. necrophorum (22.9 %, n=19) were the dominating pathogens in the 83 monobacterial PTA samples. In >60 % of the patients polymicrobial infection was demonstrated, involving a great variety of anaerobic bacteria. In 22 out of 42 cases where intravenous cefuroxime was empirically started, the therapy should be changed to properly cover the culture-proven anaerobic flora. There were no serious complications, abscess recurrence was detected in two cases (0.96 %).Conclusion. PTAs are often polymicrobial infections including a great variety of anaerobes. Targeted antibiotic therapy, in conjunction with adequate surgical drainage eliminating the anaerobic milieu, can accelerate the healing process and radically reduce the complication and recurrence rate.

Open, prospective, multicenter study on postoperative intranasal phototherapy in nasal polyposis.

BACKGROUND: The therapeutic effect of ultraviolet (UV) light is generally attributed to its immunosuppressive and immunomodulatory effects. Since chronic inflammation is the major factor in the development of nasal polyposis, we have previously used mixed ultraviolet-visible light (mUV-VIS, Rhinolight®) phototherapy for the treatment of nasal polyps. AIMS: In the present open, multicenter study, our aim was to delineate whether mUV-VIS applied postoperatively in vivo together with intranasal steroid treatment could reduce the recurrence of nasal polyps. METHODS: After functional endoscopic sinus surgery, one group of patients received mUV-VIS light together with standard intranasal steroid (mometason furoate 2 × 200 µg) application for a 12-week treatment period, whereas the other patient group obtained only intranasal steroid for the same duration. We recorded nasal endoscopy images and obtained demographical and clinical data, total nasal score (TNS), and nasal obstruction symptom evaluation (NOSE). We performed acoustic rhinometry and measured nasal inspiratory peak flow. Follow-up was 12 months. RESULTS: We found that the recurrence of nasal polyps was significantly diminished, and based on video-endoscopic measurements, the size and grade of recurrent polyps were significantly smaller in the phototherapy-receiving group. Nasal obstruction values and NOSE were significantly better throughout the follow-up period in the mUV-VIS light-treated group than in the intranasal steroid monotreatment group. CONCLUSIONS: Rhinophototherapy together with standard nasal steroid application may have a supportive role in the treatment of recurrent bilateral nasal polyps.

Tonsillectomia versus tonsillotomia / Tonsillectomia versus tonsillotomia.

Összefoglaló. Bevezetés és célkituzés: A szerzok a posztoperatív fájdalom és a sebgyógyulás tekintetében prospektív vizsgálattal hasonlították össze gyermekeken (67 fo, 1-12 év) a hagyományos hidegeszközzel történo extracapsularis tonsillectomiát (23 fo) a microdebriderrel (23 fo) és a coblatorral (21 fo) végzett intracapsularis tonsillotomiával. Módszer: A vizsgálatok a betegek által kitöltött kérdoívek, valamint prospektív klinikai adatgyujtés alapján történtek. Eredmények: Az intracapsularis tonsillotomia gyógyulási idejét 50%-kal rövidebbnek találtuk, és az elso 13 napban szignifikánsan kevesebb fájdalommal és fájdalomcsillapító igénnyel járt, mint az extracapsularis tonsillectomia eseteiben. A tonsillotomiás csoporton belül egyedül a posztoperatív elso napi fájdalom tekintetében észleltünk szignifikáns különbséget a két különbözo módszer között a coblator javára (p<0,05). A vizsgálatokat retrospektív áttekintéssel is kiegészítettük, 4 évi gyermek- (1-15 éves) tonsillamutéten átesett beteganyagunk (1487 fo) eredményeinek feldolgozásával. Tonsillectomia (1253 fo) után 7,7%-os utóvérzési arányt észleltünk, mutéti vérzéscsillapításra 1,3%-ban volt szükség. Tonsillotomia esetén (234 fo) 0,43%-os utóvérzési arányt regisztráltunk. Ebben a csoportban vérzés miatt nem, de 2 esetben ismételt obstrukciót okozó hypertrophia, 1 esetben góctünetek miatt reoperációt végeztünk (1,28%). Következtetés: Eredményeiket a szerzok a nemzetközi ajánlások tükrében elemezték. Az intracapsularis tonsillotomia kisebb fájdalommal, kisebb vérzéssel és kisebb megterheléssel jár. A közösségbe való aktív visszatérés akár egy hét után lehetséges a tonsillectomiára jellemzo 3 héttel szemben, mindez jelentos szocioökonómiai elonyökkel járhat. Orv Hetil. 2020; 161(45): 1920-1926. INTRODUCTION AND OBJECTIVE: Examining operated children in this prostective study inditerscompared (67 pts, 1-12 yrs) the extracapsular tonsillectomy with conventional cold-knife (23 pts) to extracapsular tonsillotomy with microdebrider (23 pts) and coblator (21 pts) for postoperative pain and wound-healing disorders. METHOD: The study was based on patient-completed questionnaires as well as prospective clinical data collection. RESULTS: The recovery time of intracapsular tonsillotomy was found less than 50%, with less pain than in the cases of extracapsular tonsillectomy. Postoperative pain was significantly less in the tonsillototomy group than the tonsillectomy group. Within the tonsillotomy group, a significant difference was observed between the two different methods in favor of the coblator for only the postoperative first-day pain. The studies were supplemented with a retrospective review by processing the 4 yrs results of their pediatric (1-15-yrs) patients who underwent tonsillectomy (1487 pts). After tonsillectomy (1253 pts), a postoperative bleeding rate of 7.7% was observed, and surgical hemostasis was required in 1.3%. In the case of tonsillotomy (234 pts), a postoperative bleeding rate of 0.43% was recorded. In this group, reoperation was not performed due to bleeding, whereas it was neccesary in 2 cases due to hypertrophy causing repeated obstruction, in 1 case due by virtue of focal symptomes (1.28%). CONCLUSION: Our results were analyzed on the basis of international recommendations. Intracapsular tonsillotomy is associated with less pain, less bleeding, and less strain. Active return to the community is possible after up to a week compared to the 3 weeks typical of tonsillectomy, all of which can have significant socioeconomic benefits. Orv Hetil. 2020; 161(45): 1920-1926.

The role of microbiological examination in treating peritonsillar abscess based on the retrospective analysis of data from six years / A mikrobiológiai vizsgálatok szerepe a peritonsillaris tályog kezelésében hat év anyagának retrospektív elemzése alapján.

Összefoglaló. Bevezetés és célkituzés: A peritonsillaris tályog a leggyakoribb mély nyaki infekció. Olyan fül-orr-gégészeti kórkép, amely megfelelo kezelés nélkül életveszélyes szövodményekkel járhat. Dönto jelentoségu az empirikus antibiotikumválasztás, melyhez ismerni kell a leggyakoribb kórokozókat és a várható rezisztenciát. Módszerek: A 2012 és 2017 között peritonsillaris tályog miatt kezelt esetek retrospektív feldolgozását végeztük. Összesítettük a sebészi beavatkozás során vett minták aerob és anaerob irányú tenyésztési eredményeit, valamint az empirikusan választott antibiotikumokat. A rutinszeru mikrobiológiai tenyésztés alapján meghatároztuk a leggyakoribb kórokozókat. Az adatokat nemzetközi felmérések eredményeivel hasonlítottuk össze. Eredmények: A vizsgált 6 év során 217 esetben kezeltünk peritonsillaris tályogos beteget. A tenyésztési eredményeket csak 146 esetben tudtuk elemezni. Ebbol 47 esetben került sor Fusobacterium species (ebbol 25 esetben Fusobacterium necrophorum), 31 esetben Actinomyces species és 29 esetben Streptococcus pyogenes izolálására. Az esetek kétharmadában vegyes aerob/anaerob baktériumflórát izolált a laboratórium. Következtetés: A tályogok kezelésében önmagában a sebészi beavatkozás - az anaerob környezet megszüntetésével - jelentos klinikai javulást eredményez. A jól választott antibiotikum meggyorsíthatja a lefolyást, és csökkentheti az esetleges szövodményeket. Nagy jelentosége van a megfelelo mikrobiológiai mintavételnek, nem vagy nehezen gyógyuló esetekben ez teremtheti meg a célzott antibiotikumterápiára történo váltás lehetoségét. Felmérésünk alapján a peritonsillaris tályogok jelentos részét vegyes baktériumflóra okozza, így a szájüregi anaerob baktériumokra is ható amoxicillin-klavulánsav vagy antibiotikum kombinációjának (2. vagy 3. generációs cefalosporinok kombinálva klindamicinnel vagy metronidazollal) alkalmazása javasolt mint empirikus antibiotikumterápia. Orv Hetil. 2020; 161(44): 1877-1883. INTRODUCTION AND OBJECTIVE: Peritonsillar abscess is the most common deep neck infection. Without adequate treatment, this otolaryngological disease pattern can cause life-threatening complications. The empirical choice of antibiotics is crucial which requires knowledge of the most common pathogens and the potential resistance. METHODS: A retrospective analysis of cases treated for peritonsillar abscess was performed between 2012 and 2017. We summarized the aerobic and anaerobic culture results of the surgical samples and the empirically selected antibiotics. The most common pathogens were determined via routine microbiological culture tests. We compared our data with the results of international studies. RESULTS: During the 6-year study at our Clinic, 217 patients with peritonsillar abscess were treated. The microbiological tests were available for analysis in only 146 cases. In 47 cases, Fusobacterium species (including 25 cases with Fusobacterium necrophorum), in 31 cases Actinomyces species and in 29 cases Streptococcus pyogenes were isolated. In 2/3 of the patients, polymicrobial infection was detected. CONCLUSION: In the treatment of peritonsillar abscesses, surgical intervention can result in clinical improvement because of the elimination of the anaerobic milieu. A well-chosen antibiotic can accelerate the healing process and reduce the complication rate. Proper microbiological sampling is of great importance, and in cases of non-recovery or poor recovery, this may create the opportunity to switch for targeted antibiotic therapy. The results of this study show that polymicrobial flora is very important for the development of the peritonsillar abscess, thus the recommended antibiotic therapy is amoxicillin-clavulanic acid or 2nd/3rd generation cefalosporin combined with metronidazol or clindamycin. Orv Hetil. 2020; 161(44): 1877-1883.

[Surgical treatment of laryngocele]. / Laryngokeleeseteink mutéti megoldásai.

Laryngocele is a unilateral or bilateral dilation of the saccule or appendix of the laryngeal ventricle. It is a benign lesion, often without any specific symptom, diagnosed unintentionally, but it can cause life-threatening airway obstruction, needing emergency tracheotomy. The authors present three cases of laryngocele and the related surgical methods. Orv Hetil. 2019; 160(31): 1235-1240.

[Effects of nasal provocation with a single-dose allergen on the explicit and implicit memory of physically active and inactive patients with ragweed allergy]. / Az egyszeri allergéndózis hatása az explicit-implicit emlékezetre parlagfu-allergiás sportoló és nem sportoló betegeken.

BACKGROUND AND PURPOSE: Allergy is an endemic disease and has a considerable impact on the quality of life. This study aimed to measure the effect of active allergic rhinitis on memory functions of physically active and inactive patients with ragweed allergy. METHODS: Memory functions were assessed before and after allergen exposure. Participants in both groups were provoked nasally with 30 IR/mL ragweed allergen in each nostril. Explicit memory was measured with story-recalling and implicit memory was investigated with reaction time task. RESULTS: In neuropsychological assessments athletes performed significantly better, compared with the control group after allergen provocation in short-term and long-term memory functions. There was no difference between the groups in the implicit tasks. Athletes have achieved better results after provocation, comparing to the baseline test and the tests that measured short-term and long-term memory functions. CONCLUSION: Short-term disturbing factors, e.g. swollen nasal mucosa, sneezing, and watery eyes after provocation did have not caused deterioration in cognitive functions. A single-shot allergen in high doses have caused an increase of mental concentration, which was more pronounced in athletes.

Rhinophototherapy in persistent allergic rhinitis.

Previous published results have revealed that Rhinolight® intranasal phototherapy is safe and effective in intermittent allergic rhinitis. The present objective was to assess whether phototherapy is also safe and effective in persistent allergic rhinitis. Thirty-four patients with persistent allergic rhinitis were randomized into two groups; twenty-five subjects completed the study. The Rhinolight® group was treated with a combination of UV-B, UV-A, and high-intensity visible light, while the placebo group received low-intensity visible white light intranasal phototherapy on a total of 13 occasions in 6 weeks. The assessment was based on the diary of symptoms, nasal inspiratory peak flow, quantitative smell threshold, mucociliary transport function, and ICAM-1 expression of the epithelial cells. All nasal symptom scores and nasal inspiratory peak flow measurements improved significantly in the Rhinolight® group relative to the placebo group and this finding persisted after 4 weeks of follow-up. The smell and mucociliary functions did not change significantly in either group. The number of ICAM-1 positive cells decreased non-significantly in the Rhinolight® group. No severe side-effects were reported during the treatment period. These results suggest that Rhinolight® treatment is safe and effective in persistent allergic rhinitis.

A conserved linkage group on chromosome 6, the 8.1 ancestral haplotype, is a predisposing factor of chronic rhinosinusitis associated with nasal polyposis in aspirin-sensitive Hungarians.

Inflammation plays a central role in the pathogenesis of chronic rhinosinusitis (CRS), and TNFα is a key pro-inflammatory cytokine in the pathogenesis of this disease. In our previous studies, we showed that the TNFA -308A allele is a genetic predisposition factor in a subgroup of aspirin-sensitive (ASA+) CRS patients suffering from nasal polyps (NP) in the Hungarian population. To determine whether the TNF -308A allele or the presence of a complex, extended ancestral haplotype (8.1AH) located on chromosome 6 is responsible for the previously observed genetic effect, we performed a case-control study for examining the frequency of 8.1AH carriers in controls and in subgroups of CRS patients. Our novel observations demonstrate that the presence of the 8.1AH may be responsible for the development of severe forms of CRS (CRSwNP, ASA+) and strengthen the clinical observation that CRS patients can be classified into clinically and genetically different subgroups.

The -308 G>A SNP of TNFA is a factor predisposing to chronic rhinosinusitis associated with nasal polyposis in aspirin-sensitive Hungarian individuals: conclusions of a genetic study with multiple stratifications.

Single nucleotide polymorphisms (SNPs) of the tumour necrosis factor alpha (TNFα) gene (TNFA) have been extensively studied and shown to be associated with an increased risk of the development of various chronic inflammatory diseases. Inflammation has been demonstrated to play a central role in the pathogenesis of chronic rhinosinusitis (CRS), and TNFα is a key pro-inflammatory cytokine with important functions in these processes. In order to determine whether the well-known TNFA -308 G>A SNP has a role in a genetic predisposition to CRS in the Hungarian population, we analyzed our genomic collection containing control and CRS patient samples in a case-control study, and compared the genotype and allele frequencies. There was no significant difference in the observed genotype or allele frequencies between the controls and the total CRS group. However, after careful stratification of the patient group on the basis of the observed clinical symptoms, we found a significantly higher carriage rate of the rare A allele-containing genotypes among the CRS patients with nasal polyposis (NP) who also exhibited sensitivity to aspirin (acetylsalicylic acid, ASA(+)). It is concluded that genetic variants of the TNFA gene may affect the risk of CRS in a clinically well-defined group of CRSNP(+)ASA(+) patients in the Hungarian population. Our results also emphasize that the group of CRS patients is not homogenous in that patients exhibiting different clinical symptoms exist. Their carried genetic predisposing factors, and as a result, the exact molecular events leading to the development of various forms of CRS, may also differ.

Ultraviolet light and photodynamic therapy induce apoptosis in nasal polyps.

Intranasal phototherapy has been found to be effective for the treatment of nasal polyposis (NP) therefore the aim was to investigate the apoptosis inducing effect of phototherapy in NP. In this ex vivo study nasal polyp tissue was surgically collected from 21 consecutive patients with chronic rhinosinusitis (CRS) associated with NP. The removed polyps were cut into pieces and tissue samples were irradiated in vitro by different doses of combined ultraviolet and visible light (UV/VIS: 280-650 nm) and by selective ultraviolet and visible light (sUV/VIS: 295-650 nm). Photodynamic therapy (PDT) was performed by presensitizing tissue samples with 5-delta-aminolevulinic acid (DALA) then irradiated with visible light (VIS: 395-650 nm). Tunel assay was applied to detect apoptosis of epithelial and inflammatory cells in irradiated and control nasal polyp tissue samples. UV/VIS light significantly increased epithelial cell and subepithelial leukocyte apoptosis compared to control groups. PDT treatment showed the highest surface epithelial cell as well as subepithelial leukocyte apoptosis compared to all other groups. Intranasal phototherapy may serve as a new potential therapeutical method in treatment of NP.

Antisolar halospot.

An isolated colorless spot of 1 degrees diameter located at the antisolar point was observed from a plane on the clouds beneath it. The spot can be explained by light scattering on randomly oriented ice crystals via light paths similar to those responsible for the subparhelic circle. Its peculiar polarization properties potentially permit its detection in cases where the spot is embedded in a glory.