Cyst Reduction Research Articles

Role of CFTR in Polycystic Kidney Disease

Introduction: Polycystic kidney disease (PKD) causes numerous cysts to grow in the kidneys, liver and pancreas. These cysts are filled with fluid. In the United States about 600,000 people have PKD, which is the fourth leading cause of kidney failure. The two main types of PKD are autosomal dominant PKD (ADPKD), which is usually diagnosed in adulthood and autosomal recessive PKD (ARPKD), which can be diagnosed in the womb or shortly after a baby is born. ADPKD is associated with the slow but relentless formation of multiple renal cysts. CFTR is known to be involved in secreting fluid in ADPKD through its localization in the apical membrane. Thus, the plasma membrane is the expected site where CFTR functions. Here, we show that CFTR unexpectedly is located in primary cilia and plays a role in cilia length. ARPKD is associated with systemic and portal hypertension, fibrosis of the liver and kidney and enlarged kidneys, with fusiform dilation of the collecting ducts. Although it has been postulated that CFTR plays a role in fluid secretion in ADPKD, the opposite is true in ARPKD. For example, a double mutant of CFTR and polycystin/polyductin mice develop massively enlarged kidneys and die from renal failure at ~24 days after birth (Nakanishi et. al (2001). J. Am. Soc. Nephrol. 12, 719-725). Thus, knocking down CFTR makes the disease worse. Methods: We used for ADPKD a mouse model bearing the R3277C mutation in PC1 and ARPKD mouse model bearing pkhd1Pkhd1del3-4/del3-4 deletion. We injected male and female mice with 30 mg/kg of VX-809 every other day. Also, we injected ADPKD and ARPKD mice once with AAV1 del27-264CFTR at 30 days old and sacrificed at 90 days. Results: Cyst areas are significantly reduced in kidney and liver after treatment with VX809 or with AAV1 del27-264CFTR. Conclusion: These data indicate that VX-809 reduces proliferation and the presence of CFTR at the apical membrane while increasing CFTR at the basolateral membrane in kidney in ADPKD model and liver in ARPKD model. Demonstration of kidney and liver cyst reduction increases the therapeutic potential of VX-809 as a treatment of ADPKD and ARPKD. Also we are reporting direct evidence of involvement of CFTR in cyst reduction in liver and in kidney by using gene therapy method treating ADPKD and ARPKD mice with AAV1 del27-264CFTR which would bind to WTCFTR and correct the traffcking of CFTR in ADPKD and ARPKD mice. NIH and PKD Foundation. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Optimal time to definitive enucleation of large cysts following marsupialization: A single center, retrospective study

ObjectivesOptimal time to enucleation following marsupialization of large odontogenic mandibular cysts is undefined. We aim to assess volume reduction throughout follow-up, to indicate optimal time to enucleation. Secondary objectives include the identification of factors influencing cyst reduction. Study designWe retrospectively enrolled 15 patients with mandibular cysts of different histological types treated with marsupialization at our center between 2018 and 2022. Cyst volume was assessed with cone-beam computed tomography (CBCT) and a semi-automatic segmentation algorithm, at baseline and between 6 and 8 months post marsupialization. ResultsThe overall mean cyst volume reduction percent (VR%) was 57.7 % or 0.2 % per day. VR% at 8 months was significantly higher than those assessed at 6 and 7 months (67.1% vs 47.1 %, p = 0.003). Time to CBCT was the only independent variable influencing cyst VR%. ConclusionOur study proves that the optimal time to enucleation for mandibular cyst is 8 months, independent of histological cyst type, patient age, baseline cyst volume and the number of pre-operative residual bone walls.

The dose-response relationship of subretinal gene therapy with rAAV2tYF-CB-hRS1 in a mouse model of X-linked retinoschisis.

X-linked retinoschisis (XLRS), due to loss-of-function mutations in the retinoschisin (RS1) gene, is characterized by a modest to severe decrease in visual acuity. Clinical trials for XLRS utilizing intravitreal (IVT) gene therapy showed ocular inflammation. We conducted a subretinal dose-response preclinical study using rAAV2tYF-CB-hRS1 utilizing the Rs1 knockout (Rs1-KO) mouse to investigate short- and long-term retinal rescue after subretinal gene delivery. Rs1-KO mice were subretinally injected with 2 μL of rAAV2tYF-CB-hRS1 vector with 8E9 viral genomes (vg)/eye, 8E8 vg/eye, 8E7 vg/eye, or sham injection, and compared to untreated eyes. Reconstitution of human RS1 protein was detected using western blotting. Analysis of retinal function by electroretinography (ERG) and structural analysis by optical coherence tomography (OCT) were performed at 1, 2, 3, 5, 7, and 12 months post injection (MPI). Immunohistochemistry (IHC) was performed to evaluate cone rescue on the cellular level. Functional vision was evaluated using a visually guided swim assay (VGSA). Western blotting analysis showed human RS1 protein expression in a dose-dependent manner. Quantification of western blotting showed that the RS1 protein expression in mice treated with the 8E8 vg dose was near the wild-type (WT) expression levels. ERG demonstrated dose-dependent effects: At 1 MPI the 8E8 vg dose treated eyes had higher light-adapted (LA) ERG amplitudes in 3.0 flash and 5 Hz flicker compared to untreated (p < 0.0001) and sham-treated eyes (p < 0.0001) which persisted until the 12 MPI endpoint, consistent with improved cone function. ERG b-wave amplitudes were higher in response to dark-adapted (DA) 0.01 dim flash and 3.0 standard combined response (SCR) compared to sham-treated (p < 0.01) and untreated eyes (p < 0.001) which persisted until 3 MPI, suggesting short-term improvement of the rod photoreceptors. All injections, including sham-treated, resulted in a cyst severity score of 1 (no cavities), with significant reductions compared to untreated eyes up to 3 MPI (p < 0.05). The high and low dose groups showed inconsistent ERG improvements, despite reduced cyst severity, emphasizing the dose-dependent nature of gene augmentation's efficacy and the tenuous connection between cyst reduction and ERG improvement. IHC data showed a significant cone rescue in eyes treated with the 8E8 vg dose compared to sham-treated and untreated eyes. VGSA showed better functional vision in 8E8 vg dose treated mice. Eyes treated with the highest dose showed occasional localized degeneration in the outer nuclear layer. Our data suggest that a dose of 8E8 vg/eye subretinally improves retinal function and structure in the Rs1-KO mouse. It improves cone function, rod function, and reduces cyst severity. Sham treatment resolves schisis cysts, but 8E8 vg/eye is needed for optimal retinal electrical function rescue. These findings offer a promising path for clinical translation to human trials.

Encouraging Experience with Image-Guided Pencil Beam Scanning Proton Therapy in Craniopharyngioma—First Case Series From India

PurposeTo report our early clinical experience with image-guided, pencil beam scanning proton beam therapy(PBS-PBT) for residual or recurrent craniopharyngiomas. Material and MethodsBetween September 2019 and January 2023, nineteen consecutive patients with residual, or recurrent craniopharyngioma, suitable for radiation and treated with image-guided PBS-PBT were analyzed. We documented detailed dosimetric data, acute toxicities, early outcomes and imaging response on follow-up MRI scans. ResultsA total of nineteen patients (11-males, 8-females) with residual or recurrent craniopharyngioma were treated in the given period. Median age of cohort was 14 years(range:3-33), majority constituting adamantinomatous histology(95%). Most common clinical presentation(prior to PBT) and endocrine deficit was visual disturbance(79%) and hypocortisolism(74%), respectively. Among 19, thirteen had recurrent craniopharyngioma and five of them had received radiation previously. 26% of patients(5) underwent surgery at least thrice or more before proton therapy. Median dose delivered was 54GyE. Most common acute toxicity was grade-1 alopecia(63%). None had grade-3 or above acute toxicities. With a median follow-up of 18 months(3-40 months), twelve patients showed shrinkage of residual tumor/cyst, of which, four showed dramatic cyst reduction at 3-9 months on follow-up. Two-patients had reduction in both solid and cystic components, and the remaining had reduction in cystic component only. The remaining eight patients had stable disease on MRI, with 100% disease control rate and overall survival. Visual functions remained stable post treatment. ConclusionOur preliminary experience with modern PBS-PBT and image guidance for craniopharyngioma is encouraging. Proton therapy in our cohort is well tolerated resulting in limited toxicities and promising early outcomes.

Long-term investigation of minimally invasive alcohol-based therapy as the treatment of odontogenic keratocyst:A retrospective cohort study

The aim of this study was to evaluate the clinical efficacy of alcohol-based therapy for patients with large odontogenic keratocysts (OKCs).The study was implemented as a retrospective, single-center study. Patients treated with ethanol-based therapy for odontogenic keratocyst were retrospectively evaluated for baseline and postoperative data. The pre- and postoperative clinical situation and the extent of radiographic shrinkage were compared. The event is defined as the achievement of >50% reduction in cyst volume.The cyst reduction rate calculated on panoramic radiographs ranged from 7.4% to 99.9% (mean [standard deviation] 55.3% [27.9%]) and was statistically significant (P < 0.05). Specifically, it has been found that, radiographically, 47.6% of patients achieved >50% reduction in cyst volume within 12 months. The continuous cortical bone was rebuilt, and the cyst cavity was filled with regenerated trabecular bone. The 22 included patients presented with nonclinical problems, had no need for further intervention, and exhibited persistent impaction of the teeth.The results of this study demonstrated that ethanol-based therapy triggered marked radiographic reductions of large OKC, indicating that using this technique is efficient.

Advances in the treatment of Adamantinomatous craniopharyngioma: How to balance tumor control and quality of life in the current environment: a narrative review.

Adamantinomatous craniopharyngioma (ACP) presents a significant challenge to neurosurgeons despite its benign histology due to its aggressive behavior and unique growth patterns. This narrative review explores the evolving landscape of ACP treatments and their efficacy, highlighting the continuous development in therapeutic approaches in recent years. Traditionally, complete resection was the primary treatment for ACP, but surgical -related morbidity have led to a shift. The invasive nature of the finger-like protrusions in the histological structure results in a higher recurrence rate for ACP compared to papillary craniopharyngioma (PCP), even after complete macroscopic resection. Given this, combining subtotal resection with adjuvant radiotherapy has shown potential for achieving similar tumor control rates and potentially positive endocrine effects. Simultaneously, adjuvant treatments (such as radiotherapy, intracystic treatment, and catheter implantation) following limited surgery offer alternative approaches for sustained disease control while minimizing morbidity and alleviating clinical symptoms. Additionally, advances in understanding the molecular pathways of ACP have paved the way for targeted drugs, showing promise for therapy. There is a diversity of treatment models for ACP, and determining the optimal approach remains a subject of ongoing debate in the present context. In order to achieve a good-term quality of life (QOL), the main goal of the cyst disappearance or reduction of surgical treatment is still the main. Additionally, there should be a greater emphasis on personalized treatment at this particular stage and the consideration of ACP as a potentially chronic neurosurgical condition. This review navigates the evolving landscape of ACP therapies, fostering ongoing discussions in this complex field.

КОНСЕРВАТИВНОЕ ЛЕЧЕНИЕ КИСТ МОЛОЧНЫХ ЖЕЛЕЗ: ВОЗМОЖНОСТИ ПРИМЕНЕНИЯ ПРЕПАРАТА ИНДИНОЛ ФОРТО

Among the drugs used in the conservative therapy of breast cysts and fibrocystic mastopathy, phytopreparations are mainly used in clinical practice. &#x0D; The drug Indinol Forto, obtained from plants of the cruciferous family, contains indolecarbinol, the effect of which is associated with the regulation of estrogen metabolism, inhibition of pathological proliferation, blockade of the formation of inflammatory cytokines, activation of apoptosis of transformed cells, reduction of breast cysts. The paper presents the results of a study of the pharmacological effect of the drug Indinol Forto on cystic formations of the breast. A comparative study of the use of the drug Indinol Forto showed its high effectiveness in the treatment of breast cysts, which consists in reducing the number and size of cystic formations of the breast. The drug Indinol Forto in the conservative treatment of breast cysts showed its effectiveness after 3 months of use: there was a decrease in the number of cysts (complete regression) by 3±0,5 in 13 (28,9%) patients and a partial regression of cysts with a decrease in their size by 28,7±5,8% in 16 (35,6%) patients. The optimal effect of Indinol Forto manifested itself after 6 months of use: the number of cysts decreased by 5±1,1 in 19 (42,2%) patients, and in 22 (48,9%) patients, a partial regression was noted with their reduction in size by almost half – by 49,0±7,2%. The results of the conducted studies have shown that Indinol Forto is the optimal drug that positively affects the dynamics of cystic formations of the breast. The drug Indinol Forto is well tolerated when taken orally, has no clinically identified side effects, which justifies the safety of long-term use.

Effect of Curcumin Enema Dosage Regimes on the Reduction of Giardia Cyst among Calves

Giardiasis is one of the most significant and neglected parasitic infestations among calves, resulting in intestinal infections. This protozoan agent gained diagnostic and therapeutical importance because of its zoonotic potential, in which novel alternative/substitute therapeutical interventions are important, and this is because commonly used antiparasitic drugs for control and eradication for battling this infection commonly presented side effects. Therefore, the present project evaluated the anti-protozoan activity of curcumin at different dose regimes used via the rectal route, the main constituent of turmeric. Rectal enema groups [Group I: 2 gr/kg, Group II: 80 mg/kg, and Group III: 10 mg/kg] and oral treatment Group IV: 2 gr/calf consisted of curcumin treatment at appropriate dosages showed herein in which the control group V were untreated.  All treatment groups showed a statistically significant decrease in cyst counts on day 10, compared to day 10 values of the control group (p0.005). Among the treatment groups, the highest cyst reduction was evident at 99.86% in curcumin 10 mg/kg rectal enema-administered calves (Group III), which received the lowest dose of the study.  Curcumin at all dosages, primarily used in the rectal route at the lowest dosage regimen of 10 mg/kg, could have hastened clinical and parasitological efficacy via probable inhibition of Giardia proliferation and adhesion, as described previously. This treatment modality via the rectal route can change the game, highlighting novel treatment protocols.

Prenatal dispositions and genetic analysis of monozygotic female twins with suprasellar cysts and hydrocephalus: A case report

IntroductionWe present a unique case of monozygotic female twins with virtually identical clinical and radiological presentations of supratentorial hydrocephalus and cystic formations from the suprasellar cistern.DiscussionEvaluating genetic predispositions and prenatal exposures is crucial for hydrocephalus in twins. Familial cases imply a genetic contribution to the development of these anomalies, including chromosomal abnormalities and specific variants linked to arachnoid cyst formation in various syndromes. Extensive genetic analyses found no pathogenic variants in the twins. Prenatal exposure to anti-epileptic medication was known during pregnancy and may be associated with fetal abnormalities, but not central nervous system (CNS) malformations, and was therefore not considered the cause of the condition in the twins. The twins presenting simultaneously with hydrocephalus caused by suprasellar cysts (SAC) underwent a two-step surgical management: initial ventriculoperitoneal shunt (VPS) placement followed by fenestration. Postoperative imaging showed cyst reduction, but a secondary VPS was necessary in both cases.ConclusionGenetic analysis is less likely to identify a monogenic etiology in non-syndromic cases of SACs, which are assumed to be multifactorial. There is no established evidence linking a teratogenic effect of anti-epileptic drugs to CNS malformations. Moreover, the surgical treatment of this complex condition constitutes a point of discussion.

Modulation of CXCL10 activity as a therapeutic target of ocular toxoplasmosis in diabetic mice.

Ocular toxoplasmosis is likely the most common cause of infectious posterior uveitis worldwide. CXCL10 chemokine has an important role in the maintenance of the T-cell response and the control of Toxoplasma gondii in the eye during chronic infection. Drugs that can modulate the chemokine activity could be effective against the parasite. In this work, CXCL10 local retinal expression was investigated in a diabetic mouse model with ocular toxoplasmosis for the first time. In addition, the efficacy of naphthoquinones and quinolones was compared to spiramycin (SP) in treating the infection and modulating the chemokine expression. Our results revealed that chloroquine (CQ) achieved the best results regarding the reduction of cerebral cyst burden (84.36%), improving the retinal histopathological changes, cellular infiltrates, and vasculitis significantly (P < 0.005), and balancing the strong CXCL10 expression caused by the infection. Buparvaquone-treated mice showed a significant percentage of reduction of brain cysts (76.25%), moderate improvement of histopathology, and mild to moderate CXCL10 expression. While SP showed the least efficacy against the parasite in the eye in the form of mild improvement of histopathological changes and downregulation of retinal chemokine expression with the least reduction rate of cerebral parasitic burden (57%). In conclusion, Optimal control of pathogens probably needs a balanced immune response with an optimum expression of chemokines. So, targeting the modulation of retinal CXCL10 may eventually be beneficial in the management of ocular toxoplasmosis plus its potential to act as a marker for predictive local immunological response during the infection.

Urtica dioica Extract Leads to Cyst Reduction, Enhanced Cell-Mediated Immune Response, and Antioxidant Activity in Experimental Toxoplasmosis.

Toxoplasmosis is a cosmopolitan parasitic infection caused by Toxoplasma gondii which is commonly treated by pyrimethamine (PYR) plus sulfadiazine (SDZ) with several adverse side effects. The present study evaluated the therapeutic effects of Urtica dioica L. aqueous extract (UDE) on acute and chronic toxoplasmosis in mice. For this purpose, mice were infected with 20 cysts (acute infection) or 10 cysts (chronic infection) of T. gondii (Me49 strain). The mice were treated with 200 mg/kg of UDE intraperitoneally (IP) and intragastric route (IG). The UDE-treated mice were compared with the PYR + SDZ treatment. The histopathological changes, cyst count, total antioxidant capacity (TAC), malondialdehyde (MDA) assay, and serum INF-γ were also evaluated. In the acute toxoplasmosis, UDE by IP and IG administration significantly reduced the number of brain cysts by 93.74 and 92.55%, respectively, and increased the survival rate to 80% compared with 60% in untreated controls. In the chronic infection, cyst burden decreased at 88.2 and 83.4%, respectively, for IP and IG treatments. Moreover, UDE significantly increased INF- γ levels in acute and chronic toxoplasmosis. Tissue inflammatory lesions were reduced in the UDE-treated subgroups compared to the untreated group. UDE treatment significantly reduced MDA levels and elevated TAC in both acute and chronic infections. The results show that U. dioica possesses significant immunostimulant and antioxidant activity with a higher cyst reduction in the brain during acute toxoplasmosis. Further studies are required to investigate the fractionations of UDE against T. gondii and its combination with other standard drugs.

The effects of AdipoRon on cytochrome P450-related gene expression, acute steroidogenic regulatory protein, and structure of ovary in polycystic ovary syndrome model.

One of the most common causes of infertility in adult women is polycystic ovary syndrome (PCOS) which has been identified with symptoms such as chronic hyperandrogenism, anovulation, and polycystic ovaries. Adiponectin modulates steroidogenesis and the expression of ovulation-related genes. Herein, we assessed the effect of AdipoRon (adiponectin agonist) in the PCOS model mice. The PCOS model was induced with letrozole in the adult female mice and the animals received intraperitoneal injection of AdipoRon (5 mg/kg) for 10 days. Expression of CYP11A, CYP17A, and CYP19A genes, StAR protein, and histomorphology of the ovary were evaluated using real-time RT-PCR, western blotting, and histochemistry methods, respectively. Although administration of letrozole caused an increase in the expression of CYP11A, CYP17A, and StAR and a decrease in the CYP19A1 expression, injection of AdipoRon reversed these changes. Moreover, AdipoRon treatment resulted in an improvement of folliculogenesis and a reduction of cysts compared to the letrozole-treated mice. It is likely that AdipoRon has protective effects on the PCOS through modulation of cytochrome P450-related genes and steroidogenesis but needs further study to be sure.

Long-term bone remodeling after definitive decompression for jaw cysts based on a three-dimensional analysis

BackgroundDecompression is an effective treatment for jaw cysts. Many studies have reported its effectiveness as a preliminary treatment followed by secondary enucleation. This study aimed to explore long-term bone remodeling after definitive decompression for jaw cysts based on a three-dimensional (3D) analysis. MethodsThis was a retrospective study. The clinical and radiological data of patients with jaw cysts who underwent decompression and were followed up for two years or more at Peking Union Medical College Hospital between January 2015 and December 2020 were reviewed. The 3D radiological data before and after decompression were analyzed to study the long-term reduction in cysts, especially after one year of decompression. ResultsA total of 17 patients with jaw cysts were included in this study. The radiological data showed a mean reduction rate of 78% one year after decompression. At the final examination, which was 36.1 months after decompression on average, the mean reduction rate was 86%. The unossified lesions could still ossify slowly after one year of decompression. The recurrence rate was 5.9% (1/17). ConclusionsBone remodeling continued for a long time after decompression. Definitive decompression could be an option for most patients with jaw cysts. Long-term follow-up is required.

Efficacy and safety of antiparasitic therapy for neurocysticercosis in rural Tanzania: a prospective cohort study

PurposeNeurocysticercosis is common in regions endemic for Taenia solium. Active-stage neurocysticercosis can be treated with antiparasitic medication, but so far no study on efficacy and safety has been conducted in Africa.MethodsWe conducted a prospective cohort study on treatment of neurocysticercosis in Tanzania between August 2018 and January 2022. Patients were initially treated with albendazole (15 mg/kg/d) for 10 days and followed up for 6 months. Additionally in July 2021, all participants who then still had cysts were offered a combination therapy consisting of albendazole (15 mg/kg/d) and praziquantel (50 mg/kg/d). Antiparasitic treatment was accompanied by corticosteroid medication and anti-seizure medication if the patient had experienced epileptic seizures before treatment.ResultsSixty-three patients were recruited for this study, of whom 17 had a complete follow-up after albendazole monotherapy. These patients had a total of 138 cysts at baseline, of which 58 (42%) had disappeared or calcified by the end of follow-up. The median cyst reduction was 40% (interquartile range 11–63%). Frequency of epileptic seizures reduced considerably (p < 0.001). Three patients had all active cysts resolved or calcified and of the remaining 14, eight received the combination therapy which resolved 63 of 66 cysts (95%). Adverse events were infrequent and mild to moderate during both treatment cycles.ConclusionCyst resolution was unsatisfactory with albendazole monotherapy but was very high when it was followed by a combination of albendazole and praziquantel.

Cellular mechanisms of the lufenuron growth regulator in adults of Anthonomus grandis (Coleoptera: Curculionidae)

Abstract Growth-regulating insecticides are used for several cotton pests when immature, and although not registered for Anthonomus grandis, their use causes a satisfactory population reduction in adults. However, it is not known which mechanisms are involved in this reduction. Thus, we studied which tissue and cellular changes may be involved in this process. Adults were fed with flower buds treated with lufenuron (4 ml commercial product /l) for 24 h. Then, the histology of the gonads, oxidative stress and apoptosis were evaluated after periods of 24 h and 48 h. Our study revealed that lufenuron activates the oxidative stress pathway in A. grandis, causing significant changes at the cellular level. These changes may have been caused by stimulation of the production of oxygen ions, free radicals and hydrogen peroxides, resulting in an increase in lipid peroxidation 48 h after treatment. These effects were confirmed by the presence of histopathologies in the gonads of this pest such as disorganization of the follicular cell epithelium, reduction of the yolk, disappearance of the germinal vesicle, reduction of sperm bundles and cysts. Such alterations injured the gonads and impaired tissue homeostasis. It is concluded that together these factors lead to a desirable population reduction when it comes to managing the pest in the field, because the aim is to keep it below the control level. In addition to this desired effect, it is worth noting that lufenuron is safer when compared to other commonly used products, another feature that makes its use quite interesting.

The effect of Nigella sativa oil- and wheat germ oil-loaded metal organic frameworks on chronic murine toxoplasmosis

Treatment of chronic toxoplasmosis is challenging as the available drugs are effective only in the acute stage. Therefore, the current study aimed to investigate Nigella sativa oil (NSO) and wheat germ oil (WGO) loaded on copper-benzene tricarboxylic acid metal organic framework (Cu-BTC MOF) for treating chronic toxoplasmosis in a murine model. Eighty mice were divided into 8 groups (G); uninfected untreated negative control (GI), infected untreated positive control (GII), infected and treated with: Spiramycin (GIII), Spiramycin@Cu-BTC (GIV), Cu-BTC (GV), WGO@Cu-BTC (GVI), NSO@Cu-BTC (GVII) and combined WGO+NSO@Cu-BTC (GVIII). The infected groups were orally inoculated with 10 Toxoplasma gondii Me49 strain cysts/mouse. All drugs were orally administered for 14 consecutive days starting 8 weeks post-infection (wpi). The therapeutic efficacy was evaluated by parasitological (survival rate of mice and brain cyst burden) and histopathological (brain, liver, kidney, eye) parameters. At the end of 2-weeks therapy, the highest therapeutic outcome was achieved with GVII and GVIII exhibiting 100% survival, 64.3% and 51.4% reduction of brain cysts, and an apparent amendment of pathological insults. In the next place was GVI with 90% survival, 49.5% reduction of cysts and marked amelioration of pathological lesions. Meanwhile, GIII and GIV showed 80% survival, 42.4% and 41.8% reduction of cysts as well as minimal to moderate alleviation of tissue damage. The lowest effect was obtained with GV resulting in 70% survival and 24.4% reduction of cysts. The current results support the assertion that the new metal-based nanocomposites can be promising remedies of chronic toxoplasmosis particularly if conjugated with natural herbal extracts as NSO and WGO.

Efficiacy of albendazole and paromomycin treatments against natural Giardia spp. infection in calves

The aim of the present study was to evaluate and compare the efficiacy of albendazole and paromomycine treatments against natural Giardia spp. infection in calves. The calves were divided in two groups of six animals each with similar parasitic loads of Giardiaspp. cysts. Albendazole (20 mg/kg) and paromomycin (50 mg/kg) were administrated orally to group A and group P, respectively, for three consecutive days. The efficiacies of drugs evaluated by analyzing the reduction in cyst excretion in native fecal examinations on days 0, 3, 7, 10, 14, 21 and 28. In addition, percentages of reduction for days 3, 7, 10, 14, 21 and 28 according to day 0 were evaluated. The geometric mean of fecal cyst excretion in both groups started to decrease from the 3rd day, in paromomycin group the decrease continued steadily throughout the examination days starting from the 3rd day, despite that in the albendazole group the cyst amount increased in the 7th day and then decreased again. Cyst excretion reached zero in all animals at the 21st and 28th days in group P and group A, respectively. The percentage of reduction started with a high rate of 47.72% on the third day and reached 100% on the 21st day in the paromomycin group. In the albendazole group, the percentage of reduction started with a rate of 35.29% on the third day and reached 100% on the 28th day. As a result, paromomycin was found to be more effective compared to albendazole in terms of both the regularity of the mean cyst reduction and the time it takes for the cyst excretion to reach zero.

Mefloquine loaded niosomes as a promising approach for the treatment of acute and chronic toxoplasmosis

Toxoplasmosis is a disease with a worldwide distribution and significant morbidity and mortality. In search of effective treatment, mefloquine (MQ) was repurposed and loaded with niosomes to treat acute and chronic phases of toxoplasmosis in experimental mice. Mice were orally inoculated with 20 cysts of Toxoplasma gondii (ME 49 strain) for the acute model of infection and 10 cysts for the chronic model of infection. Infected mice were dosed with MQ solution or MQ-niosomes at 50 mg/kg/day, starting from the second day post-infection (PI) (acute model) or the fifth week PI (chronic model), and this was continued for six consecutive days. The effects of MQ solution and MQ-niosomes were compared with a pyrimethamine/sulfadiazine (PYR/SDZ) dosing combination as mortality rates, brain cyst number, inflammatory score, and immunohistochemical studies that included an estimation of apoptotic cells (TUNEL assays). In the acute infection model, MQ solution and MQ-niosomes significantly reduced the mortality rate from 45% to 25 and 10%, respectively, compared with infected untreated controls, and decreased the number of brain cysts by 51.5% and 66.9%, respectively. In the chronic infection model, cyst reduction reached 80.9% and 12.3% for MQ solution and MQ-niosomes treatments, respectively. MQ-niosomes significantly decreased inflammation induced by acute or chronic T. gondii infection. Additionally, immunohistochemical analysis revealed that MQ solution and MQ-niosomes significantly increased the number of TUNEL-positive cells in brain tissue, indicative of induction of apoptosis. Collectively, these results indicate that MQ-niosomes may provide a useful delivery strategy to treat both acute and chronic toxoplasmosis.

Role of anti-Giardia recombinant cyst wall protein IgG polyclonal antibodies in diagnosis and protection

Giardia duodenalis (G. duodenalis) is an infectious protozoan that has a global distribution especially in the hot climate. Around 200 million people are infected worldwide annually by Giardia, but infection is not always accompanied by symptoms, especially in endemic countries. Using traditional microscopy techniques in diagnosis, both in stool and water samples were less sensitive when compared to immunological methods; and the need for new diagnostic methods was necessary. Also, protection from infection is required in endemic areas. Therefore, the study aimed to produce anti- G. duodenalis IgG polyclonal antibodies (pAbs) by immunizing rabbit by G. duodenalis cyst recombinant protein. The produced antibodies were evaluated in the detection of G. duodenalis antigens in patients’ stool and water samples from endemic areas across River Nile; where pAbs were used as a coating and a peroxidase conjugate antibody in sandwich ELISA. Moreover, pAbs were tested for the protection of mice from giardiasis. Sandwich ELISA using pAb has succeeded in the detection of G. duodenalis coproantigens in stool samples by a sensitivity of 97% and a specificity of 92.72%. Moreover, G. duodenalis cyst was detected in only seven water samples by ordinary microscopy; while sandwich ELISA revealed nineteen positive results. IgG pAb (1/200 µg/ml) protected mice from giardiasis; which was evident from the reduction in cysts and trophozoites numbers. We recommended the use of sandwich ELISA to monitor water quality, investigate environmental contamination and diagnosis in patients' stools. The pAbs can be prepared in large amount and used in field diagnosis and protection. This will help in the early diagnosis of G. duodenalis in water, which in turn can control outbreaks in rural areas.

Temporal sylvian fissure arachnoid cyst in children: treatment outcome following microsurgical cyst fenestration with special emphasis on cyst reduction and subdural collection

ObjectivesControversy remains regarding surgical managements of sylvian fissure arachnoid cyst (SFAC). This review presents our experience in the microsurgical fenestration of pediatric patients with SFAC to define surgical indication, and risks and benefits with special emphasis on postoperative subdural fluid collection (SDFC) and cyst size reduction.MethodsThirty-four children with SFAC who underwent microsurgical cyst fenestration at a single institution over a 10-year period were retrospectively reviewed for their clinical presentation, neuroimaging findings, and postsurgical course. The SFACs were classified by a novel grading system based on the degree of arachnoid cyst extension from the sylvian fissure to the insular cistern shown on MR images: grade 0 — little or no prominence of sylvian fissure, grade I — SFAC confined to the sylvian fissure, grade II — SFAC partially extending to the insular cistern, grade III — SFAC extending to the entire insular cistern.ResultsThere were 26 males and 8 females. SFAC was present in the left side in 24. Twelve patients presented with cyst rupturing to the subdural space. Cyst grading did not show significant difference compared with rupture status (p > 0.9). All patients underwent microsurgical cyst fenestration. Postoperative SDFC is common but often resolved overtime in two-thirds of the cases with the mean average of 6 months. However, 3 patients had symptomatic postoperative SDFC and needed reoperation shortly after the first operation. Microsurgical cyst fenestrations for SFAC effectively resolved the presenting symptoms and often showed restorations of intracranial structures on follow-up imaging. Cyst resolution or reduction greater than 75% was noted in 61.8% of the patients postoperatively which was noted in a half of the SFAC of children even with age of 11 years or older. During the follow-up, no cyst recurrence or SDFC was noted. Patients with greater surgical reduction of cyst size tended to occur in younger children, and those with lower MR grade.ConclusionOur results showed a high reduction rate of SFAC and brain re-expansion after microsurgical fenestration together with symptomatic improvements regardless the patient’s age. Considering the developing CNS during childhood, reductions of a large space-occupying lesion followed by restorations of the structural integrity of the developing brain are very desirable. However, a multi-center cooperative prospective longitudinal study on long-term comparative data of those treated and untreated of neuro-psychological outcome and cyst rupture incidence is needed.