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2.
Cureus ; 16(5): e61245, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38939274

RESUMO

INTRODUCTION: Hypertension (HTN), a leading risk factor for cardiovascular diseases, is intricately linked with endothelial dysfunction, a hallmark of vascular pathology. The effect of oxidative stress in maintaining the optimum endothelial function in the regulation of blood pressure is yet to be explored. While numerous factors contribute to the pathogenesis of HTN, emerging evidence highlights the pivotal role of oxidative stress in endothelial dysfunction, offering novel insights into the underlying mechanisms. AIM: Our study delves into the multifaceted relationship between oxidative stress and endothelial dysfunction in HTN, elucidating key molecular pathways and potential therapeutic avenues. Our study aims to find out the association between oxidative stress and endothelial function in the regulation of blood pressure. METHODS: A total of 108 age-matched participants of both genders were divided into three groups by following the guidelines of the American Heart Association (AHA) classification for HTN. Blood pressure was recorded manually in resting posture three times at an interval of 10 minutes using a sphygmomanometer after providing 10 minutes of rest before the first reading. Parameters of oxidative stress and endothelial function were measured by using a UV spectrophotometer. Our study results were depicted as mean ± SD. RESULTS: The correlation between our variables was performed using Spearman's correlation considering the value of p<0.05 as statistically significant. Serum malondialdehyde (MDA), a parameter of oxidative stress, was found to be increasing and serum nitric oxide (NO), a parameter to assess endothelial function, was found to be decreasing as the blood pressure increased. These observations are indicative that optimal oxidative stress and optimal endothelial function are required to maintain normal blood pressure regardless of gender. CONCLUSIONS: All persons who are suspected of future cardiovascular risks should be regularly checked for these parameters to avoid cardiovascular morbidity such as HTN.

3.
Biochem Biophys Res Commun ; 725: 150253, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-38880080

RESUMO

Type1 Non-specific Lipid Transfer Protein (CsLTP1) from Citrus sinensis is a small cationic protein possessing a long tunnel-like hydrophobic cavity. CsLTP1 performing membrane trafficking of lipids is a promising candidate for developing a potent drug delivery system. The present work includes in-silico studies and the evaluation of drugs binding to CsLTP1 using biophysical techniques along with the investigation of CsLTP1's ability to enhance the efficacy of drugs employing cell-based bioassays. The in-silico investigations identified Panobinostat, Vorinostat, Cetylpyridinium Chloride, and Fulvestrant with higher affinities and stability of binding to the hydrophobic pocket of CsLTP1. SPR studies revealed strong binding affinities of anticancer drugs, Panobinostat (KD = 1.40 µM) and Vorinostat (KD = 2.17 µM) to CsLTP1 along with the binding and release kinetics. CD and fluorescent spectroscopy revealed drug-induced conformational changes in CsLTP1. CsLTP1-associated drug forms showed remarkably enhanced efficacy in MCF-7 cells, representing increased cell cytotoxicity, intracellular ROS, reduced mitochondrial membrane potential, and up-regulation of proapoptotic markers than the free drugs employing qRT-PCR and western blot analysis. The findings demonstrate that CsLTP1 binds strongly to hydrophobic drugs to facilitate their transport, hence improving their therapeutic efficacy revealed by the in-vitro investigations. This study establishes an excellent foundation for developing CsLTP1-based efficient drug delivery system.


Assuntos
Antineoplásicos , Proteínas de Transporte , Citrus sinensis , Humanos , Proteínas de Transporte/metabolismo , Proteínas de Transporte/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Células MCF-7 , Citrus sinensis/química , Sistemas de Liberação de Medicamentos/métodos , Simulação de Acoplamento Molecular , Apoptose/efeitos dos fármacos , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Proteínas de Plantas/farmacologia , Ligação Proteica
4.
Indian J Otolaryngol Head Neck Surg ; 76(3): 2895-2901, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38883551

RESUMO

Myofibrosarcoma is a distinct mesenchymal malignancy which commonly occurs in head and neck region. It has a high tendency for local recurrence and distant metastasis. 39-year-old male presented with epistaxis, nasal obstruction and left sided complete loss of vision. He underwent functional endoscopic sinus surgery and guided biopsy. MRI scan showed a lesion epicentred in the left maxillary sinus, superiorly extending into the orbit. He underwent Class 4b maxillectomy with neck dissection, tracheostomy and free flap reconstruction. Histopathological examination yielded final diagnosis as myofibrosarcoma of maxilla. The patient was planned for adjuvant radiotherapy and has been disease free for 3 years.

5.
Heliyon ; 10(10): e31507, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38831819

RESUMO

Diploid inbred-based F1 hybrid True Potato Seed (DHTPS) breeding is a novel technique to transform potato breeding and cultivation across the globe. Significant efforts are being made to identify elite diploids, dihaploids and develop diploid inbred lines for heterosis exploitation in potatoes. Self-incompatibility is the first obstacle for developing inbred lines in diploid potatoes, which necessitates the introgression of a dominant S locus inhibitor gene (Sli) for switching self-incompatibility to self-compatibility. We evaluated a set of 357 diploid clones in different selfing generations for self-compatibility and degree of homozygosity using Kompetitive Allele Specific PCR (KASP) Single Nucleotide Polymorphism (SNP) markers. A subset of 10 KASP markers of the Sli candidate region on chromosome 12 showed an association with the phenotype for self-compatibility. The results revealed that the selected 10 KASP markers for the Sli gene genotype could be deployed for high throughput rapid screening of self-compatibility in diploid populations and to identify new sources of self-compatibility. The homozygosity assessed through 99 KASP markers distributed across all the chromosomes of the potato genome was 20-78 % in founder diploid clones, while different selfing generations, i.e., S0, S1, S2 and S3 observed 36.1-80.4, 56.9-82.8, 59.5-85.4 and 73.7-87.8 % average homozygosity, respectively. The diploid plants with ∼80 % homozygosity were also observed in the first selfing generation, which inferred that homozygosity assessment in the early generations itself could identify the best plants with high homozygosity to speed up the generation of diploid inbred lines.

6.
Bioorg Chem ; 149: 107473, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38820940

RESUMO

In silico approaches have been employed to design a new series of benzimidazole-containing sulphonamide derivatives and qualified compounds have been synthesized to analyze their potential as antimicrobial agents. Antibacterial screening of all synthesized compounds was done using the broth microdilution method against several human pathogenic bacteria, viz. Gram-positive bacteria [B. cerus (NCIN-2156), B. subtilis (ATCC-6051), S. aureus (NCIM-2079)] and Gram-negative bacteria [P. aeruginosa (NCIM-2036), E. coli (NCIM-2065), and a drug-resistant strain of E. coli (U-621)], and the compounds presented admirable MIC values, ranging between 100-1.56 µg/mL. The combinatorial analysis showed the magnificent inhibitory efficiency of the tested compounds, acquired equipotent to ten-fold more potency compared to original MIC values. An immense synergistic effect was exhibited by the compounds during combination studies with reference drugs chloramphenicol and sulfamethoxazole was presented as fractional inhibitory concentration (∑FIC). Enzyme inhibition studies of all synthesized compounds were done by using peptidyl transferase and dihydropteroate synthase enzymes isolated from E. coli and S. aureus and each of the compound presented the admirable IC50 values, where the lead compound 3 bound to peptidyl transferase (of S. aureus with IC50 363.51 ± 2.54 µM and E. coli IC50 1.04 ± 0.08 µM) & dihydropteroate synthase (of S. aureus IC50 3.51 ± 0.82 µM and E. coli IC50 2.77 ± 0.65 µM), might account for the antimicrobial effect, exhibited excellent inhibition potential. Antifungal screening was also performed employing food poisoning methods against several pathogenic fungal species, viz A. flavus, F. oxysporum, A. niger, and A. brassicae. The obtained result indicated that few compounds can prove to be a potent drug regimen against dreaded MDR strains of microbes. Structural activity relationship (SAR) analysis and docking studies reveal that the presence of electron-withdrawing, polar, and more lipophilic substituents positively favor the antibacterial activity, whereas, electron-withdrawing, more polar, and hydrophilic substituents favor the antifungal activities. A robust coherence has been found in in-silico and in-vitro biological screening results of the compounds.


Assuntos
Antibacterianos , Benzimidazóis , Desenho de Fármacos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Sulfonamidas , Benzimidazóis/farmacologia , Benzimidazóis/química , Benzimidazóis/síntese química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Relação Estrutura-Atividade , Sulfonamidas/química , Sulfonamidas/farmacologia , Sulfonamidas/síntese química , Estrutura Molecular , Teoria da Densidade Funcional , Relação Dose-Resposta a Droga , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Di-Hidropteroato Sintase/antagonistas & inibidores , Di-Hidropteroato Sintase/metabolismo , Humanos , Antifúngicos/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Escherichia coli/efeitos dos fármacos
7.
J Laparoendosc Adv Surg Tech A ; 34(7): 639-645, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38722056

RESUMO

Introduction: Urologic complications are thought to be the most common surgical complication of renal transplantation. Ureteral pathology, including stenosis, urine leak, and vesicoureteral reflux, predominates. Although endourologic and interventional radiological management may be utilized, failure rates remain relatively high and surgical reconstruction remains the definitive management. Robotic ureteral reconstruction has been demonstrated to provide patient benefit in nontransplant populations, but the literature on transplant reconstruction is very limited. This study reports an additional series of patients with a focus on surgical technique, as well as reviews the available evidence for robotic reconstruction for post-transplant ureteral complications. Methods: All institutional patients undergoing robotic-assisted reconstruction for post-transplant ureteral complications for the years 2019-2022 were included. Intra- and postoperative variables, patient demographics, and follow-up data were obtained retrospectively from parsing of patient records. Statistics were tabulated descriptively. Results: Eleven patients underwent ureteral reconstruction. Of the 11, 9 (81%) were male with a mean age of 51.9 years (16-70) and BMI of 33.8 (24.3-49.1). The most common (10/11) indication for reconstruction was stricture; the most common (10/11) technique used was Lich-Gregoir reimplantation. Mean operative time was 288 minutes (143-500). There were no intra- or immediate postoperative complications. Median length of stay was 2 days (1-22). There were two incidences of mortality at 2 and 5 months postoperatively unrelated to surgery. There were four readmissions within 30 days, three for urinary tract infection (UTI) and one for a pelvic abscess which required washout. The remainder of the cohort has been followed for a mean of 14.6 months (6-41) without any incidences of graft loss or recurrence of ureteral pathology. Conclusions: Robotic-assisted ureteral reconstruction is a technically challenging but highly feasible technique that may provide the benefits of minimally invasive surgery while still allowing definitive reconstruction. Centers with extensive robotic capabilities should consider the technique.


Assuntos
Transplante de Rim , Complicações Pós-Operatórias , Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Masculino , Pessoa de Meia-Idade , Feminino , Complicações Pós-Operatórias/cirurgia , Complicações Pós-Operatórias/etiologia , Transplante de Rim/efeitos adversos , Adulto , Idoso , Estudos Retrospectivos , Adolescente , Doenças Ureterais/cirurgia , Doenças Ureterais/etiologia , Adulto Jovem , Ureter/cirurgia
8.
Artigo em Inglês | MEDLINE | ID: mdl-38766821

RESUMO

Neurological disorders present a formidable challenge in healthcare, necessitating the continuous exploration of innovative therapeutic avenues. This review delves into the burgeoning field of natural diterpenoid derivatives and their promising role in addressing neurological disorders. Derived from natural sources, these compounds exhibit a diverse range of pharmacological properties, positioning them as potential agents for treating conditions such as Alzheimer's and Parkinson's disease. The review highlights recent advancements, shedding light on the multifaceted mechanisms through which diterpenoid derivatives exert their effects, from antiinflammatory to neuroprotective actions. As the scientific community navigates the translational journey from bench to bedside, integrating these natural compounds into neurotherapeutics emerges as a compelling prospect. This exploration of the therapeutic frontiers of natural diterpenoid derivatives signifies a significant step towards innovative and effective strategies in the management of neurological disorders. It highlights the potential of natural compounds to revolutionize neurotherapeutics.

9.
Biochim Biophys Acta Proteins Proteom ; 1872(4): 141015, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38615986

RESUMO

The bifunctional enzyme, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase/inosine monophosphate (IMP) cyclohydrolase (ATIC) is involved in catalyzing penultimate and final steps of purine de novo biosynthetic pathway crucial for the survival of organisms. The present study reports the characterization of ATIC from Candidatus Liberibacer asiaticus (CLasATIC) along with the identification of potential inhibitor molecules and evaluation of cell proliferative activity. CLasATIC showed both the AICAR Transformylase (AICAR TFase) activity for substrates, 10-f-THF (Km, 146.6 µM and Vmax, 0.95 µmol/min/mg) and AICAR (Km, 34.81 µM and Vmax, 0.56 µmol/min/mg) and IMP cyclohydrolase (IMPCHase) activitiy (Km, 1.81 µM and Vmax, 2.87 µmol/min/mg). The optimum pH and temperature were also identified for the enzyme activity. In-silico study has been conducted to identify potential inhibitor molecules through virtual screening and MD simulations. Out of many compounds, HNBSA, diosbulbin A and lepidine D emerged as lead compounds, exhibiting higher binding energy and stability for CLasATIC than AICAR. ITC study reports higher binding affinities for HNBSA and diosbulbin A (Kd, 12.3 µM and 34.2 µM, respectively) compared to AICAR (Kd, 83.4 µM). Likewise, DSC studies showed enhanced thermal stability for CLasATIC in the presence of inhibitors. CD and Fluorescence studies revealed significant conformational changes in CLasATIC upon binding of the inhibitors. CLasATIC demonstrated potent cell proliferative, wound healing and ROS scavenging properties evaluated by cell-based bioassays using CHO cells. This study highlights CLasATIC as a promising drug target with potential inhibitors for managing CLas and its unique cell protective, wound-healing properties for future biotechnological applications.


Assuntos
Aminoimidazol Carboxamida , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/química , Aminoimidazol Carboxamida/metabolismo , Aminoimidazol Carboxamida/farmacologia , Fosforribosilaminoimidazolcarboxamida Formiltransferase/metabolismo , Fosforribosilaminoimidazolcarboxamida Formiltransferase/química , Simulação de Acoplamento Molecular , Ribonucleotídeos/metabolismo , Ribonucleotídeos/química , Cinética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/antagonistas & inibidores , Nucleotídeo Desaminases/metabolismo , Nucleotídeo Desaminases/química , Nucleotídeo Desaminases/genética , Especificidade por Substrato , Proliferação de Células/efeitos dos fármacos , Hidroximetil e Formil Transferases/metabolismo , Hidroximetil e Formil Transferases/química , Hidroximetil e Formil Transferases/genética , Hidroximetil e Formil Transferases/antagonistas & inibidores , Complexos Multienzimáticos
10.
Laryngoscope ; 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38676455

RESUMO

INTRODUCTION: Neck dissection forms an important component in the surgical management of head and neck cancers. By using the conventional techniques of neck dissection, a conspicuous scar is inevitable for the patients. The development of robotic assisted neck dissection provides for a scar-free neck along with good oncological and functional outcomes. METHODS: A prospective observational study was conducted in our institute from 2020 March to 2022 March, where robotic-assisted neck dissections performed via the modified bilateral axillo-breast insufflation technique. RESULTS: Eighty-two patients underwent robotic neck dissections in our institute. Notably, 79 patients were treatment-naïve. The average docking time was 12 min and console time was 160 ± 15 min. The mean lymph node yield was 28.2. The average post-operative stay was 5.6 days. The average follow-up was noted to be 6.4 months. The mean cosmetic satisfaction score in our patients was 4.45. Only one patient presented with nodal recurrence, who was identified as a defaulter for adjuvant treatment. Robotic neck dissection gives similar functional and oncological outcomes as compared with conventional neck dissection. Patients had excellent cosmetic satisfaction following the procedure. The limitations of these techniques include high cost of procedure and longer operating time. This is a level IV evidence study. CONCLUSION: Although good oncological, functional, and cosmetic outcomes have been attained in robotic assisted neck dissection, further randomized controlled studies need to be conducted to justify the added costs, cosmetic advantage, and the time taken. LEVEL OF EVIDENCE: Level IV Laryngoscope, 2024.

11.
Curr Diabetes Rev ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38676505

RESUMO

The Central nervous system (CNS) is the prime regulator of signaling pathways whose function includes regulation of food intake (consumption), energy expenditure, and other metabolic responses like glycolysis, gluconeogenesis, fatty acid oxidation, and thermogenesis that have been implicated in chronic inflammatory disorders. Type 2 diabetes mellitus (T2DM) and obesity are two metabolic disorders that are linked together and have become an epidemic worldwide, thus raising significant public health concerns. Fibroblast growth factor 21 (FGF21) is an endocrine hormone with pleiotropic metabolic effects that increase insulin sensitivity and energy expenditure by elevating thermogenesis in brown or beige adipocytes, thus reducing body weight and sugar intake. In contrast, during starvation conditions, FGF21 induces its expression in the liver to initiate glucose homeostasis. Insulin resistance is one of the main anomalies caused by impaired FGF21 signaling, which also causes abnormal regulation of other signaling pathways. Tumor necrosis factor alpha (TNF-α), the cytokine released by adipocytes and inflammatory cells in response to chronic inflammation, is regarded major factor that reduces the expression of FGF21 and modulates underlying insulin resistance that causes imbalanced glucose homeostasis. This review aims to shed light on the mechanisms underlying the development of insulin resistance in obese individuals as well as the fundamental flaw in type 2 diabetes, which is malfunctioning obese adipose tissue.

12.
Indian J Otolaryngol Head Neck Surg ; 76(2): 2035-2041, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38566704

RESUMO

Venous malformations are low flow endothelial malformations with aberrant and ectatic venous channels. They are defects in vascular growth which causes functional and cosmetic impairment. Gradual growth in size of the lesion occurs due to venous congestion or thrombosis. Venous malformations in parapharyngeal space are a rare entity and are difficult to diagnose. Case Report. 13 year old boy presented with a history of hyposmia and progressive difficulty in breathing for a duration of 2.5 years. MRI face and neck with contrast showed a 4.5 × 4.3x3.6 cm lesion in the left parapharyngeal space. CT angiogram of brain and neck demonstrated a heterogeneously enhancing mass in the left parapharyngeal region. PET scan illustrated an ill-defined mass in the left pre styloid parapharyngeal space. Biopsy from the lesion showed features consistent with venolymphatic malformation. Flexible laryngoscopy showed a bulge over the left soft palate region with narrowing of nasopharyngeal lumen. Patient underwent transoral robotic surgery for complete excision of the mass. Post-operative period was uneventful. He has been on follow up for the past 1 year with no evidence of any residual or recurrent disease. Venolymphatic malformation is a rare lesion in the parapharyngeal space which is difficult to diagnose pre operatively. Surgical excision is the preferred modality of treatment for deep seated lesions in the parapharyngeal space. The advent of transoral robotic surgery have reduced the morbidity and improved clearance for such cases.

13.
Pestic Biochem Physiol ; 200: 105844, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38582571

RESUMO

Enzymes have attracted considerable scientific attention for their crucial role in detoxifying a wide range of harmful compounds. In today's global context, the extensive use of insecticides has emerged as a significant threat to the environment, sparking substantial concern. Insects, including economically important pests like Helicoverpa armigera, have developed resistance to conventional pest control methods through enzymes like carboxyl/cholinesterases. This study specifically focuses on a notable carboxyl/cholinesterase enzyme from Helicoverpa armigera (Ha006a), with the goal of harnessing its potential to combat environmental toxins. A total of six insecticides belonging to two different classes displayed varying inhibitory responses towards Ha006a, thereby rendering it effective in detoxifying a broader spectrum of insecticides. The significance of this research lies in discovering the bioremediation property of Ha006a, as it hydrolyzes synthetic pyrethroids (fenvalerate, λ-cyhalothrin and deltamethrin) and sequesters organophosphate (paraoxon ethyl, profenofos, and chlorpyrifos) insecticides. Additionally, the interaction studies between organophosphate insecticides and Ha006a helped in the fabrication of a novel electroanalytical sensor using a modified carbon paste electrode (MCPE). This sensor boasts impressive sensitivity, with detection limits of 0.019 µM, 0.15 µM, and 0.025 µM for paraoxon ethyl, profenofos, and chlorpyrifos, respectively. This study provides a comprehensive biochemical and biophysical characterization of the purified esterase Ha006a, showcasing its potential to remediate different classes of insecticides.


Assuntos
Clorpirifos , Inseticidas , Mariposas , Organotiofosfatos , Paraoxon/análogos & derivados , Piretrinas , Animais , Inseticidas/farmacologia , Inseticidas/metabolismo , Carboxilesterase/metabolismo , Helicoverpa armigera , Piretrinas/farmacologia , Piretrinas/metabolismo , Colinesterases , Resistência a Inseticidas
14.
J Vasc Surg Cases Innov Tech ; 10(3): 101469, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38577692

RESUMO

Coronavirus disease 2019-related transplant hepatic pseudoaneurysms have not been reported but can be life-threatening. They can be either solitary or multiple and can grow rapidly within weeks. They should be classified as mycotic and treated on an emergent basis. Both stenting of the vessel and coil embolization can potentially be viable treatment options of coronavirus disease 2019-related pseudoaneurysms.

15.
Indian J Surg Oncol ; 15(Suppl 1): 172-178, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38545597

RESUMO

Osteosarcomas are rare and highly malignant bone tumours which are composed of malignant mesenchymal cells producing osteoid or immature bone. Maxillary osteosarcomas are rare tumours accounting for less than 1% of head and neck malignancies. Aggressive surgical resection is the main modality of treatment with good reconstruction. Due to the complex anatomy and location of maxilla as well as its proximity to the skull, resection with negative margins is always a challenge and so is the reconstruction so as to reduce the morbidity of the patient and to also give a good functional and cosmetic outcome. Clinical outcomes can be improved with administration of neoadjuvant or adjuvant chemotherapy in selected cases and radiotherapy in case of positive margins. A 41-year-old male patient presented to the outpatient department with complaints of a bulge over the hard palate for the past 1 year. CT scan showed a 6 × 5 × 4 cm osseous expansile lesion arising from the maxillary bone. Biopsy of the tumour showed features of conventional high-grade osteosarcoma. Plate-preserving maxillectomy with tracheostomy was done followed by reconstruction with a double free flap. On post-operative day 1, the flap showed signs of venous congestion and a new free anterolateral thigh flap was done. Patient was discharged on day 7 with a Ryles tube and a tracheostomy tube in situ. Final histopathological examination showed that the tumour was a high-grade chondroblastic osteosarcoma. After regular post-operative visits in the outpatient department and evaluation with flexible laryngoscopy, patient was started on oral feed by day 10 and decannulated by day 15. He has been on regular follow-up for the past 1 year and shows no signs of recurrence or residual disease on clinical examination as well as imaging. Maxillary osteosarcoma is a rare bone tumour which requires accurate imaging and biopsy for accurate surgical planning. The ideal treatment modality is radical resection with negative margins and appropriate reconstruction. With the advent of microvascular surgery, free flaps form the backbone for reconstruction of such large defects.

16.
Indian J Otolaryngol Head Neck Surg ; 76(1): 1290-1297, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38440485

RESUMO

Introduction: Chondrosarcomas are rare malignancies of the cartilage and myxoid chondrosarcoma is its variant which commonly occurs in soft tissue of extremities. Extraskeletal chondrosarcoma is a rare malignant neoplasm of bone or soft tissue origin and is characterized by the presence of spindle cells admixed with well differentiated cartilage or chondroid stroma. They are mostly radioresistant tumours and surgical resections with adequate margins is considered as the ideal treatment modality with adjuvant radiotherapy in high grade tumours and add on chemotherapy, in case of presence of poor prognostic factors. Case Report: A 51-year-old diabetic, hypertensive female patient presented to our outpatient department with difficulty in chewing food for a duration of 6 months. On clinical examination, she had an ulceroproliferative growth involving right lower alveolus and floor of mouth. MRI face and neck with contrast showed a 4.1 × 2.9 × 4.5 cm lesion involving right lower alveolus extending to floor of mouth. Biopsy showed features of extraskeletal myxoid chondrosarcoma. She was planned for upfront surgery (Right composite resection with modified radical neck dissection with free fibula flap). Patient was stable post-surgery and was discharged in stable condition. Final histopathology report was high grade myxoid chondrosarcoma. The case was presented in tumour board and the patient was planned for adjuvant radiotherapy. She has been on regular follow up for the past 2 years and shows no signs of recurrence. Conclusion: Extraskeletal myxoid chondrosarcoma of oral cavity is a rare entity and very few cases are reported. It is a malignant neoplasm which is diagnosed with the help of immunohistochemistry. Surgery is the ideal modality of treatment accompanied by adjuvant radiotherapy in cases of high-grade tumours.

17.
Int J Biol Macromol ; 265(Pt 1): 130811, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38490399

RESUMO

Lipid Transfer Protein1 (LTP1) is a cationic, multifaceted protein belonging to the pathogenesis-related protein (PR14) family. Despite being involved in diverse physiological processes and defense mechanisms, the precise in-vivo role of LTP1 remains undiscovered. This work presents the characterization of recombinant Citrus sinensis LTP1 (CsLTP1) along with lipid binding studies through in-silico and in-vitro approaches. CsLTP1 demonstrated great thermal and pH stability with a huge biotechnological potential. It showed in-vitro binding capacity with jasmonic acid and lipids involved in regulating plant immune responses. Gene expression profiling indicated a significant upregulation of CsLTP1 in Candidatus-infected Citrus plants. CsLTP1 disrupted the cell membrane integrity of various pathogens, making it a potent antimicrobial agent. Further, in-vivo antimicrobial and insecticidal properties of CsLTP1 have been explored. The impact of exogenous CsLTP1 treatment on rice crop metabolism for managing blight disease has been studied using GC-MS. CsLTP1 triggered crucial metabolic pathways in rice plants while controlling the blight disease. CsLTP1 effectively inhibited Helicoverpa armigera larvae by impeding mid-gut α-amylase activity and obstructing its developmental stages. This study highlights the pivotal role of CsLTP1 in plant defense by offering insights for developing multi-target therapeutic agent or disease-resistant varieties to comprehensively tackle the challenges towards crop protection.


Assuntos
Anti-Infecciosos , Citrus sinensis , Citrus , Citrus sinensis/metabolismo , Proteínas de Transporte/metabolismo , Anti-Infecciosos/farmacologia , Anti-Infecciosos/metabolismo , Citrus/metabolismo
18.
Radiology ; 310(3): e232667, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38501946

RESUMO

Background Standard-of-care abscess management includes image-guided percutaneous drainage and antibiotics; however, cure rates vary, and concern for antibiotic-resistant bacteria is growing. Photodynamic therapy (PDT), which uses light-activated dyes to generate cytotoxic reactive oxygen species, could complement the standard of care by sterilizing the abscess at the time of drainage. Purpose To evaluate safety and feasibility of PDT with methylene blue (hereafter, MB-PDT) at the time of percutaneous abscess drainage. Materials and Methods This prospective, open-label, dose-escalation, first-in-humans, registered phase 1 clinical study of MB-PDT included participants who underwent percutaneous abdominal or pelvic abscess drainage with CT or US guidance from January 2015 to March 2020 and September 2022 to September 2023. Following drainage, MB-PDT was performed with laser illumination at a fluence rate of 20 mW/cm2, with fluence groups of 6, 12, 18, 24, 30, and 36 J/cm2 (n = 3 each). The primary outcome was safety, indicated by absence of fat embolism, MB escape, abscess wall damage, and need for surgery to remove optical fibers. Preliminary efficacy end points included the time to drainage catheter removal, drainage catheter output volume, and clinical symptom and fever duration. Relationships between fluence and outcomes were analyzed with Spearman correlation and linear regression analyses, and ordinary one-way analysis of variance was used for group comparisons. Results MB-PDT was safe and feasible in all 18 participants (mean age, 60.1 years ± 18.3 [SD]; 10 female), with no negative safety outcomes observed for any participant. No study-related adverse events were encountered, and the procedure did not increase reported pain (P = .1). Clinical symptom and fever duration was shorter in participants receiving higher fluences (30 and 36 J/cm2 vs 6 J/cm2) (P = .03). The presence of antibiotic-resistant bacteria was not predictive of clinical symptom and fever duration (ß = 0.13, P = .37). Conclusion MB-PDT was a safe and feasible adjunct to image-guided percutaneous abscess drainage. Clinical measures indicated a dose-dependent response to PDT. ClinicalTrials.gov registration no.: NCT02240498 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Johnston and Goldberg in this issue.


Assuntos
Abscesso , Fotoquimioterapia , Feminino , Humanos , Pessoa de Meia-Idade , Abscesso/diagnóstico por imagem , Abscesso/tratamento farmacológico , Antibacterianos , Drenagem , Estudos de Viabilidade , Estudos Prospectivos , Masculino , Adulto , Idoso
19.
Transplant Proc ; 56(2): 316-321, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38368131

RESUMO

PURPOSE: This study evaluated the effectiveness of sclerotherapy in treating lymphoceles after kidney transplantation, focusing on factors such as recurrence rates and procedural success. MATERIALS AND METHODS: Retrospective studies using sclerotherapy as the only form of treatment for postrenal transplant lymphoceles were included. All studies used percutaneous transcatheter sclerotherapy as treatment, and the success rate of the intervention was recorded. Sixty-one references were obtained by manually searching the MEDLINE (n = 20), Embase (n = 41), and Cochrane Library databases (n = 0) for retrospective research studies that included the keywords "sclerotherapy post renal transplant lymphoceles." After removing 3 duplicates, 50 of the remaining articles were excluded after the screening, and the remaining studies were extracted for demographic data and our primary outcome of the success rate of sclerotherapy. RESULTS: A descriptive analysis of the outcomes and complication rates associated with sclerotherapy interventions for lymphoceles is provided. A high degree of variation across the different studies was observed. According to the Kruskal-Wallis test, there was no correlation between the sclerosant used and the sclerotherapy complication rate (P = .472) or the success rate (P = .591). There was also no correlation between the gender of the patient and the success rate; however, there was a significant difference in the complication rate by gender (P < .005). CONCLUSIONS: In conclusion, different sclerosant products have been used for therapy with no consensus on the most efficacious product because the success rate has been variable. In addition, the gender of the patient may influence the complication rates associated with sclerotherapy for lymphoceles in patients post-kidney transplant.

20.
Phys Med Biol ; 69(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38316055

RESUMO

Photodynamic therapy (PDT) is an effective antimicrobial therapy that we used to treat human abscess cavities in a Phase 1 clinical trial. This trial included pre-PDT measurements of abscess optical properties, which affect light dose (light fluence) at the abscess wall and PDT response. This study simulated PDT treatment planning for 13 subjects that received optical spectroscopy prior to clinical PDT, to determine the impact of measured optical properties on ability to achieve fluence rate targets in 95% of the abscess wall. Retrospective treatment plans were evaluated for 3 conditions: (1) clinically delivered laser power and assumed, homogeneous optical properties, (2) clinically delivered laser power and measured, homogeneous optical properties, and (3) with patient-specific treatment planning using measured, homogeneous optical properties. Treatment plans modified delivered laser power, intra-cavity Intralipid (scatterer) concentration, and laser fiber type. Using flat-cleaved laser fibers, the proportion of subjects achieving 95% abscess wall coverage decreased significantly relative to assumed optical properties when using measured values for 4 mW cm-2(92% versus 38%,p= 0.01) and 20 mW cm-2(62% versus 15%,p= 0.04) thresholds. When measured optical properties were incorporated into treatment planning, the 4 mW cm-2target was achieved for all cases. After treatment planning, optimal Intralipid concentration across subjects was 0.14 ± 0.09%, whereas 1% was used clinically. Required laser power to achieve the 4 mW cm-2target was significantly correlated with measured abscess wall absorption (ρ= 0.7,p= 0.008), but not abscess surface area (ρ= 0.2,p= 0.53). When using spherical diffuser fibers for illumination, both optimal Intralipid concentration (p= 0.0005) and required laser power (p= 0.0002) decreased compared to flat cleaved fibers. At 0% Intralipid concentration, the 4 mW cm-2target could only be achieved for 69% of subjects for flat-cleaved fibers, compared to 100% for spherical diffusers. Based on large inter-subject variations in optical properties, individualized treatment planning is essential for abscess photodynamic therapy. (Clinical Trial Registration: The parent clinical trial from which these data were acquired is registered on ClinicalTrials.gov as 'Safety and Feasibility Study of Methylene Blue Photodynamic Therapy to Sterilize Deep Tissue Abscess Cavities,' with ClinicalTrials.gov identifier NCT02240498).


Assuntos
Fotoquimioterapia , Humanos , Fotoquimioterapia/métodos , Iluminação , Abscesso/diagnóstico por imagem , Abscesso/tratamento farmacológico , Estudos Retrospectivos , Luz , Fármacos Fotossensibilizantes/uso terapêutico
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