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1.
medRxiv ; 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39371115

RESUMEN

Objective: Planning and predicting functional outcomes of endoscopic sinus surgeries (e.g., nasal airflow) based solely on visualizing Computerized Tomography (CT) or endoscopy poses a challenge to produce optimal clinical outcomes. Study design: Technology development, retrospective case report. Methods: A virtual surgery planning (VSP) tool is developed that can load any patient's CT data and allow surgeons to remove obstructive tissue using both visual and haptic feedback endoscopically. Pre-calculated airflow resistance, wall shear stress, pressure drop are displayed on the anatomy to identify potential sites of obstruction. After each virtual surgery, changes in nasal airflow can be computed, and the process is reiterated until an optimal result is reached. Results: As proof-of-concept, a series of isolated or combined procedures were performed on CT of one patient, who had olfactory losses that may involve obstructions blocking the air/odor flow to the olfactory fossa (OF). For this patient, an isolated medial partial middle turbinectomy (PMT) demonstrated the best outcome, better than traditionally performed lateral PMT, while septal body reduction worsened air/odor flow to OF. Conclusion: This proof of concept case report demonstrates the potential usefulness of VSP in preoperative planning based on objective benchmarks and could be a valuable tool for optimizing future surgical outcomes.

2.
Lancet Infect Dis ; 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39236733

RESUMEN

BACKGROUND: Deeper insight is needed on how monoclonal antibodies (mAbs) affect vaccine-mediated immune responses when targeting the same protein. We describe the first prospective randomised trial designed to understand mAb-mediated alterations in vaccine-induced immune responses to SARS-CoV-2 spike protein epitopes. METHODS: This randomised, open-label, parallel-group study assessed the potential interaction of a mAb combination, casirivimab and imdevimab, with a vaccine, Moderna's mRNA-1273, in healthy SARS-CoV-2 immunologically naive, seronegative adults at six centres in the USA. Participants were randomly assigned (per prespecified randomisation ratios within enrolment waves) according to a computer-generated randomisation scheme, stratified by age (<65 years and ≥65 years), to various intravenous or subcutaneous doses of casirivimab and imdevimab before, after, or at the same time as mRNA-1273 or to mRNA-1273 only. The doses of casirivimab and imdevimab were chosen to mimic various time intervals between receipt of 1200 mg of the mAb and the first dose of a primary series with mRNA-1273. The primary endpoint was vaccine-induced 50% inhibitory dilution neutralising antibody titres to SARS-CoV-2 spike protein, 56 days after the first vaccination. Secondary endpoints included vaccine-induced total antibodies to SARS-CoV-2 antigens and incidence of treatment-emergent adverse events. Exploratory endpoints included blood-derived T-cell and B-cell responses. The per-protocol set was used for the analysis of the primary endpoint and included all randomly assigned participants who received both doses of the vaccine and completed the injection or infusion of casirivimab and imdevimab per protocol, had no evidence of SARS-CoV-2 infection in the past or in the 56 days after the first dose of vaccine, and did not receive any intervention outside of the study that could alter the immune response. Safety was assessed in the safety analysis set, which included all randomly assigned participants who had received one or more doses of mRNA-1273 or any study drug, and analysed based on treatment received. The study is registered with ClinicalTrials.gov, NCT04852978, and is complete. FINDINGS: Between April 29, 2021, and Nov 21, 2022, 807 participants were assessed for eligibility and 295 were randomly assigned. 293 participants were included in the safety analysis set and 260 were included in the per-protocol set. All vaccinated participants developed neutralising antibodies to SARS-CoV-2, with median titres above the published protective threshold (100 IU/mL) against the SARS-CoV-2 D614G variant (considered a reference strain at the time the initial COVID-19 vaccines were developed). Titres were decreased up to 4-fold (median titres 280-450 IU/mL for casirivimab and imdevimab vs 1160 IU/mL for vaccine only on day 56) when casirivimab and imdevimab was given 85 days or less before vaccination (150-1200 mg intravenously) or co-administered subcutaneously (600 mg or 1200 mg) with vaccination. Minimal reduction in neutralisation titres was observed in the 48 mg and 12 mg intravenous groups, corresponding to receipt of casirivimab and imdevimab 113 days and 169 days, respectively, before vaccination, and when administering the vaccine 6 days before the mAb. Across all groups, mAbs had a minimal effect on vaccine-induced total antibodies and T-cell responses to the spike protein. Casirivimab and imdevimab plus mRNA-1273 was generally well tolerated; a slight increase in treatment-emergent adverse events was observed in the casirivimab and imdevimab plus vaccine groups versus the vaccine-only group. INTERPRETATION: Casirivimab and imdevimab administration before or at the time of COVID-19 vaccination reduced the elicitation of SARS-CoV-2 neutralising antibodies, but minimal effect was observed when vaccination occurred before mAb administration. Although the clinical significance of this decrease in neutralisation is unclear, this evidence suggests that further investigation of potential interactions could be warranted before concurrent clinical use of mAbs and vaccines targeting the same viral proteins as their main modes of action for the prevention or treatment of infectious diseases. FUNDING: Regeneron Pharmaceuticals and F Hoffmann-La Roche.

3.
Laryngoscope ; 2024 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-39305211

RESUMEN

INTRODUCTION: Computational fluid dynamic (CFD) modeling has previously indicated that distorted nasal airflow patterns may contribute to empty nose syndrome (ENS); however, no data show that aggressive turbinate surgery always leads to ENS. We aim to use virtual surgery planning (VSP) to investigate how a total inferior turbinectomy affects airflow parameters compared with ENS patients. METHODS: We retrospectively recruited six nasal obstruction patients who underwent turbinate reduction surgery. We virtually performed total inferior turbinectomy on these patients to compare CFD modeling results to patients' actual surgical outcomes and to that of a previously collected ENS patient cohort (n = 27). RESULTS: Patients' actual surgery outcomes were excellent, with Nasal-Obstruction Symptom Evaluation (NOSE) score (pre: 72.5 ± 13.2 vs post-surgery: 10.8 ± 9.8, p < 0.001) and unilateral visual analog scale (VAS) scores of nasal obstruction (pre: 6 ± 2.56 vs post-surgery: 1.2 ± 1, p < 0.001) improved and was statistically significant. The virtual turbinectomy does not create the same distorted nasal airflow patterns as seen in ENS patients, with no statistically significant difference in nasal resistance as compared with post-actual surgery (virtual turbinectomy: 0.10 ± 0.03 Pa/mL*s; actual surgery: 0.12 ± 0.04 Pa/mL*s; ENS: 0.11 ± 0.04, p > 0.05) nor in regional wall shear force distribution, an important indicator of air/mucosa stimulation (inferior turbinate WSF%: virtual 47.3% ± 11.3% vs actual 51.5% ± 15.1%, p > 0.05); however, both are statistically significant higher than that of ENS patients (WSF: 32.2% ± 12.5%, p < 0.001), despite ENS cohort having wider inferior airway cross-sectional area (CSA) than actual surgeries. CONCLUSION: Empty nose syndrome is likely a multifactorial disease process that cannot be solely attributed to aggressive turbinate reduction surgery. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

4.
Folia Morphol (Warsz) ; 83(1): 215-220, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-36688406

RESUMEN

A 77-year-old female cadaver was observed to have a rare branching pattern of the right axillary artery (AA). The first part of the AA typically gives off only a superior thoracic artery (STA) but was observed to give off three branches in the case: a lateral thoracic artery (LTA), a thoracoacromial trunk, and a large common trunk (CT). The LTA travelled to provide a variant STA to the 1st and 2nd intercostal spaces. The CT provided an accessory LTA and accessory thoracodorsal artery before bifurcating into a subscapular artery (SA) and posterior humeral circumflex artery. As expected, the SA further divided into the circumflex scapular artery and thoracodorsal artery. A pectoral artery and the anterior humeral circumflex artery originated directly from the second and third parts of the AA, respectively. Knowledge of AA branching variations is of great clinical significance to anatomists, radiologists, and surgeons due to the high rate of injury to this artery.


Asunto(s)
Brazo , Arteria Axilar , Femenino , Humanos , Anciano , Húmero , Cadáver , Conocimiento
5.
J Opioid Manag ; 19(4): 343-364, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37644792

RESUMEN

OBJECTIVE: To review the current literature surrounding the relationship between adverse childhood experiences (ACEs) and opioid use disorder (OUD) to guide clinical identification of high-risk individuals and assess treatment implications. DESIGN: A PubMed search was conducted from the year 2000 to 2022 using a series of primary and secondary search terms. A total of 21,524 unique results were screened for relevancy to ACEs and OUDs. After excluding unrelated articles, a total of 48 articles were included in this systematic review. RESULTS: Increased frequency of ACEs was directly related to increased risk of OUD and lower onset age. ACEs were also associated with OUD severity. ACEs linked to OUD included childhood neglect, emotional abuse, physical abuse, and sexual abuse. Additionally, dysfunctional childhood home environment, female gender, and psychiatric/behavioral comorbidities increased the risk of OUD, while resilience was found to be a protective factor. Multiple biochemical markers were associated with both ACEs and OUD. CONCLUSIONS: Children experiencing multiple ACEs should be the target of preventative intervention by medical professionals. Clinicians should include ACEs in their opioid misuse risk assessment. High incidence of co-occurring psychiatric/behavioral disorders provides multiple treatment avenues for patients with OUD. Resilience, along with being therapy target, should be fostered early in the life course. Incorporation of family members may improve opioid abuse treatment outcomes. Future research should focus on interventions interrupting the progression of ACEs to OUD along with proposed biochemical pathways.


Asunto(s)
Experiencias Adversas de la Infancia , Trastornos Relacionados con Opioides , Niño , Humanos , Femenino , Analgésicos Opioides/efectos adversos , Medición de Riesgo , Trastornos Relacionados con Opioides/epidemiología , Trastornos Relacionados con Opioides/psicología
6.
BMJ Case Rep ; 16(2)2023 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-36796872

RESUMEN

Internal hernias are protrusions of viscera that can cause obstructions such as small bowel obstruction (SBO). Diagnosis can be challenging, as they usually come with an atypical presentation. We report on a case of a woman in her early 40s, with no history of surgery or chronic illnesses, which came with abdominal pain associated with vomiting. CT scan revealed obstructed small bowel. On exploratory laparoscopy, an internal hernia through a peritoneal defect in the vesicouterine space was found, entrapping a limb of the jejunum. The entrapped loop of the small bowel was freed, the ischaemic part was resected, and the defect was closed. Our case presents the second reported case of a congenital vesicouterine defect causing SBO. It is important to consider patients presenting with SBO as a case of congenital peritoneal defect if they had no previous surgeries.


Asunto(s)
Hernia Abdominal , Obstrucción Intestinal , Laparoscopía , Femenino , Humanos , Hernia Abdominal/complicaciones , Hernia Abdominal/diagnóstico por imagen , Obstrucción Intestinal/diagnóstico por imagen , Obstrucción Intestinal/etiología , Obstrucción Intestinal/cirugía , Hernia Interna/cirugía , Peritoneo , Laparoscopía/efectos adversos , Hernia/complicaciones , Hernia/diagnóstico por imagen
7.
Cureus ; 14(7): e27021, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35989853

RESUMEN

Introduction Diabetes and coronavirus disease 2019 (COVID-19) are interrelated. The presence of hyperglycemia per se during COVID-19 infection regardless of diabetes status has been associated with poor prognosis and increased risk of mortality. Objectives The main aim of the current study was to assess the association between admission hyperglycemia and COVID-19 outcomes. Methods This is a retrospective cohort study including 315 patients, mainly employed in the facility, who presented to the emergency department or were admitted with confirmed COVID-19 infection from April 2020 to August 2021. Results The mean age of the studied cohort was 40.2±12.5 years, where 59.68% were males and 37.7% were symptomatic. Older age, male gender, history of diabetes and hypertension, and elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH) levels were associated with a significantly increased risk of developing cytokine release syndrome (CRS). Admission hyperglycemia was significantly associated with poor outcomes. The time to negativity was 9.30±0.1 days for asymptomatic patients; however, it increased significantly according to clinical presentation, presence of comorbidities, and severe outcomes, in patients with cytokine release syndrome. Conclusions Admission hyperglycemia was associated with an increased risk of progression to critical condition in patients hospitalized with COVID-19 independent of the history of diabetes. Therefore, it should not be overlooked but instead should be detected and appropriately treated to improve outcomes. In addition, post-COVID-19 care should be individualized, where severe cases require almost double the time needed by mild cases to convert to negative.

8.
Cureus ; 14(2): e22582, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35371821

RESUMEN

Nontraumatic splenic rupture and hematoma are rare in sickle cell disease. We present a case of a 22-year-old Saudi male with sickle cell disease. He presented to our hospital with a history of nontraumatic abdominal pain, hemodynamic instability, and abdominal tenderness, with a large mass extending to the umbilicus. A computed tomography (CT) examination showed splenomegaly and a spleen infarction. The patient was admitted to the intensive care unit (ICU) and stabilized. He was transferred to the regular ward and discharged against medical advice (DAMA). Later on, he presented again with persistent abdominal pain. He underwent splenectomy with cholecystectomy. The patient did well postoperatively and was discharged in good condition. While conservative management is common, operative management should be considered in patient with persistent pain. Splenic rupture has a high mortality rate.

9.
Cureus ; 14(2): e22304, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35350481

RESUMEN

Lipomas are slow-growing, benign mesenchymal masses. Most lipomas are small, weighing only a few grams; however, if their size becomes exceptionally large, they are called giant lipomas. Giant lipoma of the breast is infrequently observed due to the rarity of size and location, with very few case reports available in the literature. Here, we report the case of a 48-year-old female patient who presented with a painless, huge lump in her right breast. The patient underwent surgical removal of the mass with a histologic examination confirming the diagnosis of a giant breast lipoma.

10.
Otol Neurotol Open ; 2(4): e022, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38516575

RESUMEN

Objective: To describe the experiences of patients who elected for the active surveillance treatment option for their vestibular schwannoma (VS). Study Design: Twenty-two patients participated in semistructured patient interviews. Setting: Interviews were conducted between March and April 2021 via telephone with audio recordings and notes taken during each interview. Patients: Adults diagnosed with a VS and at any point after their diagnosis underwent a period of active surveillance were recruited based on the diagnosis made by MRI. Patients were excluded if they chose to undergo treatment immediately, had a diagnosis of neurofibromatosis type 2, or if they had a confirmed alternative diagnosis. Intervention: This intervention was a qualitative interview to assess patient experiences with their VS treatment decision. Main Outcome Measures: Identifying abstract categories that represent many of the stories told by the participants that produces a theory grounded in the data with explanatory power. Results: Factors that influenced patients' treatment decisions were perceived physician bias, selfeducation, and personal accounts of VS patients through support groups, and side effects/complications of the various treatment options. Conclusion: Patients who opted for active surveillance as a treatment option reported high satisfaction with their decision and greater confidence in future treatments that would be necessary based on tumor growth. Future work should be done to increase shared decision making between the physician and patient to arrive at a treatment plan that aligns with their goals of care as well as potentially reducing overtreatment of VS.

11.
Cureus ; 13(10): e19028, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34824938

RESUMEN

Malaria presents a challenge to healthcare systems globally. It is associated with severe complications, notably splenic rupture. The prognosis of malaria complicated by splenic rupture is poor and sometimes leads to death even with timely intervention. Here, we report the case of a patient who presented with complicated malaria with spontaneous splenic rupture and coincidental acute appendicitis. A 34-year-old man was successfully treated for a grade IV ruptured spleen and acute appendicitis with splenectomy and appendectomy. Postoperative care took place in the intensive care unit and the patient was shifted to the general floor on the fifth day. Upon discharge the next day, he was prescribed amoxicillin twice daily for one year. Malaria can present with life-threatening complications requiring prompt surgical intervention.

12.
Cureus ; 13(8): e17135, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34532173

RESUMEN

Rectal procidentia is an uncommon perineal disease that is rare in males. There is no specific medical role in treatment of rectal procidentia and surgical intervention is the treatment of choice. Various surgical approaches have been performed, but there is no consensus on which procedure is most effective in terms of patient condition, recurrence rate, bowel function, and risk. This case presentation of a healthy male patient with experience of uncomplicated reducible rectal prolapse and a history of chronic constipation. Presented with complicated rectal prolapse in the presence of incarcerated rectal prolapse after a failed trial with conservative maneuvers, he ended up with abdominal approach sigmoidectomy and posterior mesh rectopexy.

13.
Cureus ; 13(6): e16042, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34336523

RESUMEN

Flood syndrome is a spontaneous rupture of an umbilical hernia. It has a high mortality and morbidity and presents many challenges in medical versus surgical management. We present a case of a 23-year-old Yamani woman with complicated umbilical hernia, newly diagnosed hepatitis B infection, and decompensated liver cirrhosis with ascites (Child-Pugh grade B). The patient was undergoing multiple abdominal ascitic tapping that eventually ruptured with an omentum evisceration, causing Flood syndrome. An urgent umbilical hernioplasty with mesh in a sublay technique was conducted.

14.
Cureus ; 13(12): e20625, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35106195

RESUMEN

Acute cholecystitis is a very common acute abdominal disease that mostly indicates abdominal surgery. Appendiceal adhesion to the gallbladder is a very rare condition detected during laparoscopic surgery. A 54-year-old female patient, with a known case of diabetes and hypertension, presented with right upper quadrant abdominal pain of four months' duration. The pain was increasing in severity and associated with fatty meals. She was diagnosed with acute cholecystitis and was sent to the operating room for laparoscopic cholecystectomy. Appendiceal adhesion to the gallbladder was found, and laparoscopic cholecystectomy and laparoscopic appendectomy were performed. Adhesion of the appendix to the gallbladder should be considered by general surgeons.

15.
Gen Thorac Cardiovasc Surg ; 69(3): 487-496, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32979148

RESUMEN

OBJECTIVES: To evaluate perioperative risk factors for AF in patients undergoing uniportal VATS pneumonectomy versus open thoracotomy, and to investigate mediastinal lymph nodes dissection (MLND) on the occurrence of AF. METHODS: Patients were divided into 2 groups based on the surgical approach: uniportal VATS and open pneumonectomy. Analysis was done using chi-square test. Multiple variables were tested using univariate analysis. A p value ≤ 0.05 was considered statistically significant. RESULTS: Three-hundred and forty-one patients underwent pneumonectomy between 2014 and 2018 in Shanghai Pulmonary Hospital. Fifty-eight patients underwent uniportal VATS, and 283 underwent thoracotomies. AF was the most common event observed. The overall occurrence of peri-operative AF was 33/341 (9.67%). In the uniportal, converted, and open group the incidence of AF was: 3/52 (5.76%), 1/6 (16.6%), and 29/283 (10.42%), respectively. Overall, there was no specific surgical technique correlated with increased incidence of AF (p = 0.432). By univariate analysis; large tumor size > 4.5 cm (p < 0.010), operative time (OT) > 125 min (p < 0.002), and greater volume of blood loss (p < 0.001) increased the risk of AF. Additionally, patients who experienced higher post-operative pain (p < 0.002) were more vulnerable to developing AF. Mortality occurred in one AF patient (1/33, 3%). Number of lymph nodes harvested was not related to AF incidence (p = 0.520). CONCLUSIONS: Although AF incidence was lower in uniportal group, it was not statistically significant. Large tumor size, long operative time, and increased blood loss were associated with increased risk of perioperative AF. These results need to be confirmed by larger studies.


Asunto(s)
Fibrilación Atrial , Neoplasias Pulmonares , Fibrilación Atrial/epidemiología , China/epidemiología , Humanos , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/cirugía , Neumonectomía/efectos adversos , Complicaciones Posoperatorias , Estudios Retrospectivos , Factores de Riesgo , Cirugía Torácica Asistida por Video/efectos adversos , Toracotomía/efectos adversos
16.
Microorganisms ; 7(12)2019 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-31817071

RESUMEN

We previously discovered that single nucleotide polymorphisms (SNPs) in PTPN2/22 (T-cell negative-regulators) occur in 78% of rheumatoid arthritis (RA), along with Mycobacterium avium paratuberculosis (MAP) infection in 33% of patients. In Crohn's disease, we reported that SNPs in TNFα and receptors (TNFRSF1A/TNFRSF1B) benefited intracellular MAP-survival, increased infection, and elevated inflammatory response mimicking the poor response to anti-TNFα treatment in some patients. Here, we studied the frequency and effects of SNPs in TNFα/TNFRSF1A/TNFRSF1B in RA including gene expression, MAP infection, and osteoporosis marker levels in blood (54 RA and 48 healthy controls). TNFα:rs1800629 (GA) was detected in 19/48 (40%) RA and 8/54 (15%) controls (p-value < 0.05, odds ratio (OR) = 3.6, 95% CI: 1.37-9.54). TNFRS1B:rs3397 (CT) was detected in 21/48 (44%) RA and 10/54 (19%) controls (p-value < 0.05, OR = 4.43, 95% CI: 1.73-11.33). In RA, rs3397 downregulated TNFRSF1B expression (CC > CT (0.34 ± 0.14) and CC > TT (0.27 ± 0.12)), compared to wildtype CC (0.51 ± 0.17), p-value < 0.05. MAP DNA was detected significantly in 17/48 (35.4%) RA compared to 11/54 (20.4%) controls (p-value < 0.05, OR = 2.14, 95% CI: 1.12-5.20). The average osteocalcin level was significantly lower (p-value < 0.05) in RA (2.70 ± 0.87 ng/mL), RA + MAP (0.60 ± 0.31 ng/mL), RA + TNFRSF1B:rs3397 (TT) (0.67 ± 0.35 ng/mL), compared to the healthy control (5.31 ± 1.39 ng/mL), and MAP-free RA (3.85 ± 1.31 ng/mL). Overall, rs3397 appears to downregulate TNFRSF1B, increase MAP infection, worsen inflammation, and cause osteocalcin deficiency and possibly osteoporosis in RA.

17.
Gen Thorac Cardiovasc Surg ; 67(11): 991-995, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30799520

RESUMEN

The behavior of the pathological subtypes of tracheal glomus tumor (benign, uncertain malignant potential UMP, malignant) is vague. In a 51-year-old gentleman, suffering from cough for 4 months, computed tomography scan showed a mass at lower third of the trachea and the bronchoscope revealed exophytic mass at the tracheal lumen. Segmental tracheal resection was done using special modified endotracheal tube for the distal lung ventilation. The tracheal glomus tumor was also diagnosed based on the immunohistochemical staining. The tumor was 2 cm in diameter, deeply located, mitotic phase was difficult to identify, and a diagnosis of UMP subtype was made. There was no recurrence after 2 years follow-up. This is the first reported case of UMP subtype in lower trachea and we studied the treatment options with the clinic-pathological behavior of this tumor and its sequel by regular follow-up.


Asunto(s)
Tumor Glómico/patología , Tumor Glómico/cirugía , Neoplasias de la Tráquea/patología , Neoplasias de la Tráquea/cirugía , Tumor Glómico/diagnóstico por imagen , Humanos , Intubación Intratraqueal/instrumentación , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Neoplasias de la Tráquea/diagnóstico por imagen
18.
PLoS One ; 9(9): e108238, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25250732

RESUMEN

Mitochondria play a key role in aerobic ATP production and redox control. They harness crucial metabolic pathways and control cell death mechanisms, properties that make these organelles essential for survival of most eukaryotic cells. Cancer cells have altered cell death pathways and typically show a shift towards anaerobic glycolysis for energy production, factors which point to mitochondria as potential culprits in cancer development. Targeting mitochondria is an attractive approach to tumor control, but design of pharmaceutical agents based on rational approaches is still not well established. The aim of this study was to investigate which structural features of specially designed Zn(II)N-alkylpyridylporphyrins would direct them to mitochondria and to particular mitochondrial targets. Since Zn(II)N-alkylpyridylporphyrins can act as highly efficient photosensitizers, their localization can be confirmed by photodamage to particular mitochondrial components. Using cultured LS174T adenocarcinoma cells, we found that subcellular distribution of Zn-porphyrins is directed by the nature of the substituents attached to the meso pyridyl nitrogens at the porphyrin ring. Increasing the length of the aliphatic chain from one carbon (methyl) to six carbons (hexyl) increased mitochondrial uptake of the compounds. Such modifications also affected sub-mitochondrial distribution of the Zn-porphyrins. The amphiphilic hexyl derivative (ZnTnHex-2-PyP) localized in the vicinity of cytochrome c oxidase complex, causing its inactivation during illumination. Photoinactivation of critical cellular targets explains the superior efficiency of the hexyl derivative in causing mitochondrial photodamage, and suppressing cellular respiration and survival. Design of potent photosensitizers and redox-active scavengers of free radicals should take into consideration not only selective organelle uptake and localization, but also selective targeting of critical macromolecular structures.


Asunto(s)
Mitocondrias/metabolismo , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Porfirinas/química , Porfirinas/farmacología , Zinc/química , Zinc/farmacología , Animales , Línea Celular Tumoral , Respiración de la Célula/efectos de los fármacos , Complejo IV de Transporte de Electrones/antagonistas & inhibidores , Complejo IV de Transporte de Electrones/metabolismo , Humanos , Mitocondrias/efectos de los fármacos , Fármacos Fotosensibilizantes/farmacocinética , Porfirinas/farmacocinética , Ratas , Zinc/farmacocinética
19.
Dalton Trans ; 43(47): 17666-76, 2014 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-25154705

RESUMEN

Ultrafast excited-state dynamics of planar Pt, Pd, and Ni dithione-dithiolato complexes were investigated by transient absorption spectroscopy on the femtosecond-picosecond timescale. All studied complexes show a common photobehaviour, although individual kinetics parameters and quantum yields vary with the metal, the dithione ligand and, namely the solvent (DMF, MeCN). Laser pulse irradiation at 800 nm populates the lowest singlet excited state of a dithiolato → dithione charge transfer character, (1)LL'CT. The optically excited state undergoes a solvation-driven sub-picosecond electronic relaxation that enhances the dithione/dithiolato charge separation. The (1)LL'CT state decays with a 1.9-4.5 ps lifetime by two simultaneous pathways: intersystem crossing (ISC) to the lowest triplet state (3)LL'CT and non-radiative decay to the ground state. ISC occurs on a ∼6 ps timescale, virtually independent of the metal, whereas the rate of the non-radiative decay to the ground state decreases on going from Ni (2 ps) to Pd (3 ps) and Pt (∼10 ps). (3)LL'CT is initially formed as a vibrationally excited state. Its equilibration (cooling) takes place on a picosecond timescale and is accompanied by a competitive decay to the ground state. Equilibrated (3)LL'CT is populated with a quantum yield of less than 50%, depending on the metal: Pt > Pd > Ni. (3)LL'CT is long-lived for Pt and Pd (≫500 ps) and short-lived for Ni (∼15 ps). Some of the investigated complexes also exhibit spectral changes due to vibrational cooling of the singlet (2-3 ps, depending on the solvent). Rotational diffusion occurs with lifetimes in the 120-200 ps range. Changing the dithione (Bz2pipdt/(i)Pr2pipdt) as well as dithiolate/diselenolate (dmit/dsit) ligands has only small effects on the photobehavior. It is proposed that the investigated dithione-dithiolato complexes could act as photooxidants (*E(o) ≈ +1.2 V vs. NHE) utilizing their lowest excited singlet ((1)LL'CT), provided that the excited-state electron transfer is ultrafast, competitive with the picosecond decay. On the other hand, the efficiency of any triplet-based processes would be severely limited by the low quantum yield of the triplet population.

20.
Saudi Med J ; 28(3): 379-81, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17334463

RESUMEN

OBJECTIVE: Helicobacter pylori (H. pylori) is an important etiological factor in the development of upper gastro intestinal tract (GIT) conditions. A variety of tests are now available to diagnose H. pylori infection but they require a relatively longer time to yield a definitive result. The present work describes fast agar-based urease (FABU) test for detection of the H. pylori in gastric biopsy. METHODS: One hundred and eighty-seven patients with upper GIT conditions were included in this study for the period from April 2003 to May 2004. One antral biopsy was taken from 100 patients while 2 antral biopsies were taken from 87 patients and inserted into FABU test, in addition to 3-4 biopsies were taken for histology examination. RESULTS: Using one antral biopsy, the FABU test correctly identified 65 of the 78 biopsies positive for H. pylori by histology (83.3%). There were 11 false negative (FN) and 3 false positive (FP). This yields sensitivity of 85.5% and specificity of 87.5%. While when 2 antral biopsies were used, the test correctly identified 61 of 64 H. pylori infected patients (92.2%). There were 3 FP and 5 FN. This yields sensitivity of 92.4% and specificity of 85.7%. Also, the result of this study revealed that 73.2% of the total patients included in this study were infected with H. pylori. Approximately 46.5% were males and 26.7% were females. CONCLUSION: The results of our study indicate that the FABU test is superior to other commercially available urease tests and provides rapid results of H. pylori status even before the patient is discharged from endoscopy suite.


Asunto(s)
Infecciones por Helicobacter/patología , Helicobacter pylori/aislamiento & purificación , Úlcera Gástrica/diagnóstico , Ureasa/metabolismo , Biopsia con Aguja , Estudios de Cohortes , Femenino , Mucosa Gástrica/microbiología , Mucosa Gástrica/patología , Infecciones por Helicobacter/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Inmunohistoquímica , Masculino , Juego de Reactivos para Diagnóstico , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Úlcera Gástrica/microbiología
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