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1.
J Cell Mol Med ; 28(18): e70116, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39340487

ABSTRACT

Global impact of viral diseases specially Monkeypox (mpox) and Marburg virus, emphasizing the urgent need for effective drug interventions. Oxymatrine is an alkaloid which has been selected and modified using various functional groups to enhance its efficacy. The modifications were evaluated using various computatioanal analysis such as pass prediction, molecular docking, ADMET, and molecular dynamic simulation. Mpox and Marburg virus were chosen as target diseases based on their maximum pass prediction spectrum against viral disease. After that, molecular docking, dynamic simulation, DFT, calculation and ADMET prediction were determined. The main objective of this study was to enhance the efficacy of oxymatrine derivatives through functional group modifications and computational analyses to develop effective drug candidates against mpox and Marburg viruses. The calculated binding affinities indicated strong interactions against both mpox virus and Marburg virus. After that, the molecular dynamic simulation was conducted at 100 ns, which confirmed the stability of the binding interactions between the modified oxymatrine derivatives and target proteins. Then, the modified oxymatrine derivatives conducted theoretical ADMET profiling, which demonstrated their potential for effective drug development. Moreover, HOMO-LUMO calculation was performed to understand the chemical reactivity and physicochemical properties of compounds. This computational analysis indicated that modified oxymatrine derivatives for the treatment of mpox and Marburg virus suggested effective drug candidates based on their binding affinity, drug-like properties, stability and chemical reactivity. However, further experimental validation is necessary to confirm their clinical value and efficacy as therapeutic candidates.


Subject(s)
Alkaloids , Antiviral Agents , Drug Design , Marburgvirus , Molecular Docking Simulation , Molecular Dynamics Simulation , Quinolizines , Alkaloids/chemistry , Alkaloids/pharmacology , Quinolizines/chemistry , Quinolizines/pharmacology , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Marburgvirus/drug effects , Animals , Humans , Matrines
2.
Pediatr Res ; 2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38177248

ABSTRACT

BACKGROUND: Given the sparse data on the renin-angiotensin system (RAS) and its biological effector molecules ACE1 and ACE2 in pediatric COVID-19 cases, we investigated whether the ACE1 insertion/deletion (I/D) polymorphism could be a genetic marker for susceptibility to COVID-19 in Egyptian children and adolescents. METHODS: This was a case-control study included four hundred sixty patients diagnosed with COVID-19, and 460 well-matched healthy control children and adolescents. The I/D polymorphism (rs1799752) in the ACE1 gene was genotyped by polymerase chain reaction (PCR), meanwhile the ACE serum concentrations were assessed by ELISA. RESULTS: The ACE1 D/D genotype and Deletion allele were significantly more represented in patients with COVID-19 compared to the control group (55% vs. 28%; OR = 2.4; [95% CI: 1.46-3.95]; for the DD genotype; P = 0.002) and (68% vs. 52.5%; OR: 1.93; [95% CI: 1.49-2.5] for the D allele; P = 0.032). The presence of ACE1 D/D genotype was an independent risk factor for severe COVID-19 among studied patients (adjusted OR: 2.6; [95% CI: 1.6-9.7]; P < 0.001. CONCLUSIONS: The ACE1 insertion/deletion polymorphism may confer susceptibility to SARS-CoV-2 infection in Egyptian children and adolescents. IMPACT: Recent studies suggested a crucial role of renin-angiotensin system and its biological effector molecules ACE1 and ACE2 in the pathogenesis and progression of COVID-19. To our knowledge, ours is the first study to investigate the association of ACE1 I/D polymorphism and susceptibility to COVID-19 in Caucasian children and adolescents. The presence of the ACE1 D/D genotype or ACE1 Deletion allele may confer susceptibility to SARS-CoV-2 infection and being associated with higher ACE serum levels; may constitute independent risk factors for severe COVID-19. The ACE1 I/D genotyping help design further clinical trials reconsidering RAS-pathway antagonists to achieve more efficient targeted therapies.

3.
Pediatr Res ; 93(5): 1383-1390, 2023 04.
Article in English | MEDLINE | ID: mdl-36085364

ABSTRACT

BACKGROUND: Given the sparse data on vitamin D status in pediatric COVID-19, we investigated whether vitamin D deficiency could be a risk factor for susceptibility to COVID-19 in Egyptian children and adolescents. We also investigated whether vitamin D receptor (VDR) FokI polymorphism could be a genetic marker for COVID-19 susceptibility. METHODS: One hundred and eighty patients diagnosed to have COVID-19 and 200 matched control children and adolescents were recruited. Patients were laboratory confirmed as SARS-CoV-2 positive by real-time RT-PCR. All participants were genotyped for VDR Fok1 polymorphism by RT-PCR. Vitamin D status was defined as sufficient for serum 25(OH) D at least 30 ng/mL, insufficient at 21-29 ng/mL, deficient at <20 ng/mL. RESULTS: Ninety-four patients (52%) had low vitamin D levels with 74 (41%) being deficient and 20 (11%) had vitamin D insufficiency. Vitamin D deficiency was associated with 2.6-fold increased risk for COVID-19 (OR = 2.6; [95% CI 1.96-4.9]; P = 0.002. The FokI FF genotype was significantly more represented in patients compared to control group (OR = 4.05; [95% CI: 1.95-8.55]; P < 0.001). CONCLUSIONS: Vitamin D deficiency and VDR Fok I polymorphism may constitute independent risk factors for susceptibility to COVID-19 in Egyptian children and adolescents. IMPACT: Vitamin D deficiency could be a modifiable risk factor for COVID-19 in children and adolescents because of its immune-modulatory action. To our knowledge, ours is the first such study to investigate the VDR Fok I polymorphism in Caucasian children and adolescents with COVID-19. Vitamin D deficiency and the VDR Fok I polymorphism may constitute independent risk factors for susceptibility to COVID-19 in Egyptian children and adolescents. Clinical trials should be urgently conducted to test for causality and to evaluate the efficacy of vitamin D supplementation for prophylaxis and treatment of COVID-19 taking into account the VDR polymorphisms.


Subject(s)
COVID-19 , Receptors, Calcitriol , Vitamin D Deficiency , Adolescent , Child , Humans , COVID-19/genetics , Genetic Predisposition to Disease , Genotype , Receptors, Calcitriol/genetics , Risk Factors , SARS-CoV-2 , Vitamin D , Vitamin D Deficiency/complications , Vitamin D Deficiency/genetics
4.
Mol Biol Rep ; 50(12): 9887-9895, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37864661

ABSTRACT

BACKGROUND: Tramadol is one of the most commonly abused substances in the Middle East. Furthermore, smoking is extremely common among the population. METHODS: An experimental study was performed on Sprague-Dawley rats to explore the effects of both nicotine and tramadol on the liver and testes. The tramadol was administered at 10 and 20 mg/kg, respectively, while the nicotine was administered at 125 mg/kg. Histological examination and androgen receptor ELISA assay showed mild effects on the liver and proofed safety on the testis. Western blot analysis of BIP (immunoglobulin heavy-chain binding protein) and CHOP (CCAAT-enhancer-binding protein homologous protein) revealed that fewer problems were induced by adding nicotine to tramadol. Autophagy marker LCIII and apoptosis marker caspase-8 showed similar effects to CHOP and BIP on liver samples. The real-time PCR of BIP expression showed similar but not identical results. CONCLUSIONS: The results showed mild endoplasmic reticulum stress, autophagy, and apoptosis in the liver samples. Histological examination revealed stable spermatogenesis with average androgen receptor blood levels in the different groups.


Subject(s)
Testis , Tramadol , Rats , Male , Animals , Nicotine/pharmacology , Tramadol/metabolism , Tramadol/pharmacology , Receptors, Androgen/genetics , Receptors, Androgen/metabolism , Rats, Sprague-Dawley , Liver/metabolism , Apoptosis , Endoplasmic Reticulum Chaperone BiP , Endoplasmic Reticulum Stress
5.
Anim Biotechnol ; 34(7): 2414-2419, 2023 Dec.
Article in English | MEDLINE | ID: mdl-35801402

ABSTRACT

The main objectives of this study were to estimate genetic parameters for the survival, longevity and evaluate risk factors for the occurrence of mortality in a Japanese quail line selected for high growth rate during the period from hatch to 21 days of age (GR1-21) for eight generations and its control. Total number of 1095, 2289 and 16,506 for sires, dams and progeny, respectively, was used to estimate genetic parameters, a separate hatch of 687 chicks was used to examine the risk factors of quails in the selected (SL, 438) and control (CL, 249) lines. The proportion of censored quails until 42 days of age was 82.20 and 87.14 for SL and CL, respectively. The CL showed higher longevity than SL (38.42 vs. 36.86 days). In the two tested lines, mortality% significantly declined when body weight at death increased, however, the CL had a higher reduction of mortality% than the SL (50 vs. 42%). Survival and longevity had low heritability values, low genetic and phenotypic correlations between survival and longevity with GR1-21 and ranging from 0.025 to 0.208. The survival tended to be less correlated with GR1-21 and body weight at marketing age than the longevity.


Subject(s)
Coturnix , Animals , Coturnix/genetics , Phenotype , Body Weight/genetics
6.
Mediators Inflamm ; 2022: 3300903, 2022.
Article in English | MEDLINE | ID: mdl-36248189

ABSTRACT

Neurodegenerative disorders are marked by neuronal death over time, causing a variety of cognitive and motor dysfunctions. Protein misfolding, neuroinflammation, and mitochondrial and protein clearance system dysfunction have all been identified as common pathways leading to neurodegeneration in recent decades. An altered microbiome of the gut, which is considered to play a central role in diseases as well as health, has recently been identified as another potential feature seen in neurodegenerative disorders. An array of microbial molecules that are released in the digestive tract may mediate gut-brain connections and permeate many organ systems, including the nervous system. Furthermore, recent findings from clinical as well as preclinical trials suggest that the microbiota of the gut plays a critical part in gut-brain interplay and that a misbalance in the composition of the gut microbiome may be linked to the etiology of neurological disorders (majorly neurodegenerative health problems); the underlying mechanism of which is still unknown. The review aims to consider the association between the microbiota of the gut and neurodegenerative disorders, as well as to add to our understanding of the significance of the gut microbiome in neurodegeneration and the mechanisms that underlie it. Knowing the mechanisms behind the gut microbiome's role and abundance will provide us with new insights that could lead to novel therapeutic strategies.


Subject(s)
Gastrointestinal Microbiome , Microbiota , Neurodegenerative Diseases , Brain , Gastrointestinal Microbiome/physiology , Humans
7.
Parasitol Res ; 121(1): 35-48, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34842987

ABSTRACT

New antiparasitic drugs are urgently required for treating parasitic infections. The marine environment has proven to be a valuable source of compounds with therapeutic properties against many diseases, including parasitic diseases. Cnidarian venoms are known for their toxicological properties and are candidates for developing medications. In this review, the antiparasitic properties of cnidarian toxins, discovered over the last two decades, were examined. A total of 61 cnidarian compounds from 18 different genera of cnidaria were studied for their antiparasitic activities. The assessed genera belonged mainly to three geographical areas: South America, North America, and Southeast Asia. The in vitro activities of crude extracts and compounds against a range of parasites including Plasmodium falciparum, Trypanosoma brucei gambiense, T. cruzi, T. congolense, Leishmania donovani, L. chagasi, L. braziliensis, and Giardia duodenalis are reviewed. The challenges involved in developing these compounds into effective drugs are discussed.


Subject(s)
Cnidaria , Leishmania donovani , Animals , Antiparasitic Agents , Parasitic Sensitivity Tests , Plasmodium falciparum
8.
Qatar Med J ; 2022(2): 18, 2022.
Article in English | MEDLINE | ID: mdl-35909399

ABSTRACT

BACKGROUND: Patients undergoing hemodialysis are exposed to various potential allergens from medication, dialysis catheters, topical antiseptics, and different adhesive dressings. Many patients develop a local allergic reaction and get itchy rashes, which may get infected, leading to significant morbidity and preventable health cost. In this study, we aimed to report the incidence of contact dermatitis (CD) and its potential complications in hemodialysis (HD) patients at the Al Wakra Hospital Dialysis unit. METHODS: We performed a retrospective chart review of documented local allergic reactions at vascular access sites for the HD patients at the Al Wakra Hospital. RESULTS: Currently, 102 patients are getting maintenance HD through catheters or arteriovenous (AV) fistula. Twelve (14.4%) patients developed CD (7 [58%] had cuffed jugular dialysis catheter, and 5 [42%] had an AV fistula). Most patients (75%) developed CD in the early period of dialysis initiation, and 25% developed it later in the course. Most patients responded to removing adhesive plasters and dressing the vascular access site using gauze only and topical steroids (hydrocortisone 1% cream/mometasone 0.1% cream). Two (16.6%) of the 12 patients developed vascular access site infection, of whom 1 had an AV fistula and developed a severe rash with cellulitis leading to sepsis and 2 admissions, although blood cultures remained negative. The patient responded to IV antibiotics and local mometasone 0.1% cream. Complete removal of all adhesive tapes helped prevent recurrence of the rash. Later, dressing of the AV fistula site was performed only with a cotton gauze. The second patient had a jugular catheter and developed an allergic rash leading to cellulitis and tunnel infection. Swab culture showed Staphylococcus aureus from the exit site sensitive to cloxacillin/cefazolin. The patient improved after local and oral antibiotics and removal of adhesive tapes. The catheter was not removed, and the patient did well. CONCLUSION: The incidence of CD at our dialysis unit is 14.4%. Previously published reports from other dialysis units showed a lower incidence of 1.25%. Early identification and diagnosis of allergic rash at the vascular access site and avoidance of adhesive plasters and other potential allergens prevent complications like infection and loss of precious vascular accesses in these patients.

9.
Prostate ; 81(4): 223-230, 2021 03.
Article in English | MEDLINE | ID: mdl-33471385

ABSTRACT

OBJECTIVE: To compare the oncologic outcomes of radical prostatectomy (RP) versus external beam radiotherapy (EBRT) ± androgen deprivation therapy for primary treatment of high risk localized prostate cancer (CaP). METHODS: We retrospectively reviewed a prospectively-populated database for cases who underwent primary treatment for high risk localized CaP, had more than 2 years follow-up, and were treated since 2006. A total of 335 cases were studied of whom 291 underwent RP and 44 underwent EBRT. Clinical characteristics, biochemical progression-free survival (BPFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS) were compared. RESULTS: EBRT cases were older (p < .01; mean 71 years vs. 61 years) and had longer PSA doubling time (PSADT) (p = .03; median 4.8 years vs. 3.5 years) than RP. Race, pretreatment PSA and biopsy Gleason score were similar. Median follow-up was 5.1 (range: 2.3-12.8) years for RP versus 3.3 (range: 2-12.4) years for EBRT. Three- and 5-year BPFS were 42% and 36% after RP versus 86% and 75% after EBRT (p < .01). The rate of adjuvant/salvage therapy was 58% after RP versus 20% after EBRT (p < .01). Three- and 5-year MFS were 80% and 77% after RP versus 91% and 91% after EBRT (p = .11). Three-year CSS was 98% in both groups and OS was 97% after RP versus 94% after EBRT (p = .73). CONCLUSIONS: RP had higher rates of biochemical failure and adjuvant or salvage treatment versus EBRT in high risk localized CaP. MFS trended toward benefit after EBRT, but CSS and OS remained high in both groups.


Subject(s)
Androgen Antagonists/therapeutic use , Prostate-Specific Antigen/blood , Prostate/pathology , Prostatectomy , Prostatic Neoplasms , Radiotherapy , Aged , Biopsy/methods , Combined Modality Therapy/methods , Combined Modality Therapy/statistics & numerical data , Databases, Factual/statistics & numerical data , Humans , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , Prostatectomy/methods , Prostatectomy/statistics & numerical data , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/surgery , Radiotherapy/methods , Radiotherapy/statistics & numerical data , Risk Adjustment/methods , Salvage Therapy/methods , Salvage Therapy/statistics & numerical data , Survival Analysis , United States/epidemiology
10.
Lupus ; 29(7): 767-775, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32380889

ABSTRACT

BACKGROUND: Recently, the interleukin-17A (IL-17A) gene has emerged as a potential candidate gene for autoimmune disorders, including systemic lupus erythematosus (SLE). OBJECTIVES: This study aimed to investigate whether IL-17A polymorphisms at rs2275913 G/A, rs8193036 C/T and rs3748067 C/T could be susceptibility markers for juvenile-onset SLE (JSLE) and lupus nephritis (LN) in Egyptian children and adolescents. METHODS: In this multi-centre study, we genotyped 320 patients diagnosed with JSLE and 320 matched control children for three IL-17A polymorphisms at rs2275913 G/A, rs8193036 C/T and rs3748067 C/T using TaqMan probe-based real-time polymerase chain reaction. Meanwhile, IL-17A serum levels were assessed using ELISA. RESULTS: The IL-17 rs2275913 A/A genotype and A allele were more represented in JSLE patients compared to the control group (21% vs. 7%, odds ratio (OR) = 3.8, 95% confidence interval (CI) 1.78-5.5, p = 0.001, pBonf = 0.003 for the A/A genotype; 37% vs. 29%, OR = 1.4, 95% CI 1.11-1.8, p = 0.003, pBonf = 0.009 for the A allele. No significant difference was found for IL-17 rs8193036 and rs3748067 single nucleotide polymorphisms (SNPs) in genotype distribution or allele frequencies (p>0.05). Patients carrying the IL-17 rs2275913 A/A genotype and A allele were more likely to develop LN (OR = 5.64, 95% CI 2.39-13.77, pBonf = 0.001 for the A/A genotype; OR = 2.73, 95% CI 1.84-4.07, pBonf = 0.02 for the A allele). CONCLUSION: The IL-17 rs2275913 A allele and A/A genotype were associated with high IL-17 serum levels and may contribute to susceptibility to JSLE and the development of LN in Egyptian children and adolescents. However, no significant association was evident between the studied IL-17A SNPs and other clinical phenotypes, disease activity scores or laboratory profile of JSLE.


Subject(s)
Genetic Predisposition to Disease , Interleukin-17/genetics , Lupus Erythematosus, Systemic/genetics , Lupus Nephritis/genetics , Polymorphism, Single Nucleotide , Adolescent , Alleles , Case-Control Studies , Child , Egypt , Female , Gene Frequency , Humans , Logistic Models , Lupus Erythematosus, Systemic/pathology , Lupus Nephritis/pathology , Male , Prospective Studies , Risk Factors
11.
Mar Drugs ; 18(12)2020 Dec 10.
Article in English | MEDLINE | ID: mdl-33322046

ABSTRACT

Six new (1, 2, 6, 8, 13, and 20) and twenty previously isolated (3-5, 7, 9-12, 14-19, and 21-26) steroids featuring thirteen different carbocycle motifs were isolated from the organic extract of the soft coral Sinularia polydactyla collected from the Hurghada reef in the Red Sea. The structures and the relative configurations of the isolated natural products have been determined based on extensive analysis of their NMR and MS data. The cytotoxic, anti-inflammatory, anti-angiogenic, and neuroprotective activity of compounds 3-7, 9-12, 14-20, and 22-26, as well as their effect on androgen receptor-regulated transcription was evaluated in vitro in human tumor and non-cancerous cells. Steroids 22 and 23 showed significant cytotoxicity in the low micromolar range against the HeLa and MCF7 cancer cell lines, while migration of endothelial cells was inhibited by compounds 11, 12, 22, and 23 at 20 µM. The results of the androgen receptor (AR) reporter assay showed that compound 11 exhibited the strongest inhibition of AR at 10 µM, while it is noteworthy that steroids 10, 16, and 20 displayed increased inhibition of AR with decreasing concentrations. Additionally, compounds 11 and 23 showed neuroprotective activity on neuron-like SH-SY5Y cells.


Subject(s)
Anthozoa/chemistry , Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents/pharmacology , Neuroprotective Agents/pharmacology , Steroids/pharmacology , Angiogenesis Inhibitors/isolation & purification , Angiogenesis Inhibitors/pharmacology , Animals , Anti-Inflammatory Agents/isolation & purification , Antineoplastic Agents/isolation & purification , Cell Survival/drug effects , HeLa Cells , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Indian Ocean , MCF-7 Cells , Molecular Structure , Neoplasms/drug therapy , Neoplasms/metabolism , Neoplasms/pathology , Neovascularization, Physiologic/drug effects , Neurons/drug effects , Neurons/metabolism , Neurons/pathology , Neuroprotective Agents/isolation & purification , Steroids/isolation & purification , Structure-Activity Relationship
12.
J Toxicol Pathol ; 33(2): 87-95, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32425341

ABSTRACT

This study investigated the protective effects of minocycline against acrylamide (ACR)-induced neurotoxicity and testicular damage in Sprague-Dawley rats. Forty rats were divided into five groups (eight rats each). Group I received saline (0.5 mL/rat) daily for 10 days and served as the untreated control group. Group II received ACR (30 mg/kg body weight (b.w.)) daily for 10 days. Group III received ACR (30 mg/kg b.w.) daily for 10 days and subsequently minocycline (60 mg/kg b.w.) for five days. Group IV received ACR (30 mg/kg b.w.) daily for 10 days followed by saline for five days and served as the control group for the ACR-minocycline-treated group. Group V received minocycline (60 mg/kg b.w.) for five days. All treatments were administered orally. Rats in group I and V showed normal locomotor behavior and normal histology of the brain and testes. Administration of ACR (Group II and IV) resulted in weight loss and gait abnormalities. Furthermore, neuronal degeneration in the hippocampus and cerebellum and degeneration of the seminiferous tubular epithelium with formation of spermatid giant cells were observed. Ultrastructurally, ACR specifically damaged spermatogonia and spermatocytes. Acrylamide was also seen to cause a significant increase of malondialdehyde levels in the brain and testes. Treatment of ACR-administered rats with minocycline (Group III) significantly alleviated the loss of body weight and improved locomotor function. Minocycline also ameliorated neuronal degeneration and seminiferous tubular damage and decreased malondialdehyde concentrations. In conclusion, minocycline protects against neurotoxic effects of acrylamide and seminiferous tubular damage. Decreasing lipid peroxidation by minocycline might play a role in such protection.

13.
Ultrastruct Pathol ; 42(3): 255-261, 2018.
Article in English | MEDLINE | ID: mdl-29565703

ABSTRACT

Medicinal plants have recently gained increasing scientific interest as an important source of molecules with different therapeutic potentials. Accordingly, the present study was carried out to investigate ultrastructural changes induced by the aqueous extract of Solanum incanum (SI) fruit on human colorectal carcinoma cell line (HCT 116 cells). Examination of SI-treated HCT 116 cells with transmission electron microscopy (TEM) demonstrated numerous ultrastructural changes in the form of loss of the surface microvilli, mitochondrial damage and dilatation of cristae, and formation of autophagic vacuoles and increasing numbers of lipid droplets. Also, majority of the treated cells showed nuclear shrinkage with chromatin condensation and nucleolar changes. Moreover, some cells showed focal areas of cytoplasmic degeneration associating with formation of myelin figures and fatty globules. In conclusion, TEM was able to verify cytotoxicity of SI aqueous extract against HCT 116 colon cancer cells.


Subject(s)
Antineoplastic Agents/pharmacology , Colonic Neoplasms/ultrastructure , Plant Extracts/pharmacology , Apoptosis/drug effects , Cell Proliferation/drug effects , Fruit , HCT116 Cells , Humans , Microscopy, Electron, Transmission , Solanum
14.
Ultrastruct Pathol ; 42(4): 358-364, 2018.
Article in English | MEDLINE | ID: mdl-29952682

ABSTRACT

Injury to lacrimal glands represents a major health problem after radiation therapy of the head and neck malignancies. Accordingly, this study aimed to investigate significant ultrastructural changes of lacrimal glands and some of their underlying mechanisms following the exposure to different fractionated doses of irradiation. In this study, 28 Sprague Dawley (SD) rats were assigned to four groups (seven rats each): Group I acted as control and received no irradiation. Groups II-IV received fractionated irradiation of 5 Gy (100 cGy/fraction daily for 5 days), 9 Gy (300 cGy/fraction daily for 3 days), and 20 Gy (one fraction), respectively. One month after the experiment, examination of lacrimal glands with transmission electron microscopy (TEM) demonstrated dose-dependent ultrastructural changes in the lacrimal acinar and intralobular ductal epithelial cells. In the acinar cells, there were swollen rough endoplasmic reticulum, irregularly shaped nuclei with chromatin condensation, mitochondrial damage, and retention of secretory granules. Intaralobular ductal epithelial cells showed loss of surface microvilli and damage to mitochondria. In addition to the potential direct effects of irradiation on lacrimal acinar and intralobular ductal epithelial cells, damage to blood vessels and nerve endings seemed to mediate some of the underlying mechanisms of these irradiation-induced ultrastructural changes. In conclusion, using TEM reveals that lacrimal gland is highly sensitive to even small doses of irradiation therapy; in addition, swelling of rough endoplasmic reticulum and aberrant nuclei are the most encountered structural changes. Damage to blood vessels and nerve endings might mediate some of the underlying mechanisms of irradiation-induced secondary injury in lacrimal glands.


Subject(s)
Endoplasmic Reticulum, Rough/ultrastructure , Lacrimal Apparatus/radiation effects , Lacrimal Apparatus/ultrastructure , Mitochondria/ultrastructure , Radiation Injuries , Animals , Cell Nucleus/ultrastructure , Microscopy, Electron, Transmission , Rats, Sprague-Dawley
15.
Ann Plast Surg ; 80(3): 272-276, 2018 Mar.
Article in English | MEDLINE | ID: mdl-28984656

ABSTRACT

The peroneus brevis flap was first described as proximally based by Mathes et al (Surg Clin North Am. 1974;54:1337-1354) and later by Jackson and Scheker (Injury. 1982;13:324-330). A distally based version of this flap by Mathes and Nahai (Reconstructive Surgery: Principles, Anatomy and Technique. 1997:1437e46) was subsequently described in 1997. The first case series of distally based flaps was published by Eren et al (Plast Reconstr Surg. 2001;107:1443-1448). In our experience, the distally based flap is a useful muscle flap to reconstruct small defects in the lateral distal third of the leg. Initial interest and confidence in the use of this flap in our unit were hindered by lack of direct experience and descriptive detail in the literature. We have now developed a systematic approach to harvest the distally pedicled peroneus brevis muscle flap in 5 reproducible, safe steps. This has allowed the flap to become adopted as a standard technique of limb reconstruction in our unit with no cases of flap loss.


Subject(s)
Leg Injuries/surgery , Muscle, Skeletal/transplantation , Soft Tissue Injuries/surgery , Surgical Flaps/transplantation , Humans , Muscle, Skeletal/blood supply , Plastic Surgery Procedures/methods , Surgical Flaps/blood supply
17.
J Hand Microsurg ; 16(4): 100065, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39234389

ABSTRACT

Background: Free flap reconstruction of the lower extremity is technically challenging and may suffer from higher complication rates than other anatomical sites. One important vascular consideration in the reconstructive process is the microsurgical anastomotic technique, namely whether an end-to-end (ETE) or end-to side (ETS) technique is used. The ETS technique is often preferred by lower limb microsurgeons, who describe its benefits of improved distal perfusion. However, this preference remains based on individual experience or poor evidence. Methods: A systematic review of the evidence was performed, with inclusion of specifically traumatic lower limb wounds requiring free tissue transfer. Flap failure was utilised as the primary outcome, with secondary outcomes including thrombosis. Results: Six articles, with 1153 microvascular anastomoses were included. Meta-analysis results revealed no statistical significance in flap failure when comparing ETS to ETE (OR 0.72, CI 0.45-1.15). Included articles were limited by study design (case series) and therefore only provided level IV evidence. Conclusion: Although further research is required to elucidate the outcomes of both microvascular anastomotic techniques, the results of this review and the wider literature at present do not provide support for any microvascular anastomotic technique over the other.

18.
Injury ; 55(2): 111234, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38029681

ABSTRACT

INTRODUCTION: Enhanced recovery (ER) aims to achieve earlier recovery, reduced hospital length of stay (LoS) whilst improving outcomes. Our ER protocol for acute lower-limb open fracture (ALLOFs) includes dangling at day 3 and mobilising fully weight-bearing from day 5. Our aims were to evaluate the outcomes of ALLOFs using our ER protocol for limb salvage, LoS following 'fix & flap', return to theatre, rate of successful flap salvage, flap failure and deep infection rates. METHODS: An observational study of a prospectively maintained lower limb flap database from September 2020 to January 2023 was undertaken. Search criteria encompassed patients with a Gustilo IIIB/C injury and a free flap reconstruction. Exclusions were for local/perforator flaps, soft tissue injury only, fracture related/prosthetic joint infections, or chronic osteomyelitis cases. RESULTS: 161 patients were available for analysis, 126 male (78 %) and 35 female (22 %) with a median age of 40 years (12-79, interquartile range 30.0). 81 % of cases were high-energy injuries. For all patients, the median time to definitive fixation and soft tissue coverage from injury was 4 days (0-30, interquartile range 2). 18 cases (11.2 %) required return to theatre for flap exploration; 11 cases were successfully salvaged (61 %). Nine free flaps failed (5.4 %). The median total LoS from admission was 10 days (6 to 46, interquartile range 5), with a median LoS following definitive fixation and soft tissue coverage of 7 days (4 to 20, interquartile range 3). The median follow-up period was 18 months (12 to 38.2, interquartile range 9), with a deep infection rate of 6.5 %. CONCLUSION: In isolated ALLOFs, our ER protocol is safe and effective in shortening the LoS. Our outcomes sit comfortably within acceptable ranges of contemporary literature for return to theatre, flap salvage/failure and deep infection. Our ER protocol actively involves our allied health professional colleagues early to facilitate discharge.


Subject(s)
Fractures, Open , Free Tissue Flaps , Soft Tissue Injuries , Tibial Fractures , Adult , Female , Humans , Male , Fracture Fixation, Internal/methods , Fractures, Open/surgery , Lower Extremity/surgery , Lower Extremity/injuries , Postoperative Complications , Soft Tissue Injuries/surgery , Surgical Wound Infection/surgery , Tibial Fractures/surgery , Treatment Outcome
19.
J Orofac Orthop ; 85(Suppl 2): 208-222, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38748283

ABSTRACT

OBJECTIVES: This study aimed to analyze the global scholarly production of articles related to temporary anchorage devices (TADs) from 1998-2023 in peer-reviewed dental journals indexed in the Web of Science. MATERIALS AND METHODS: A database of TADs-related articles was created via a Web of Sciences structured search. The bibliometric characteristics of the studies, including the number of citations, publication year, journal title, journal impact factor (IF), authorship, contributing institutions and countries, thematic field, and study design, were extracted. Keyword co-occurrence network analyses and the correlation between the number of citations and the article age, journal IF, and journal quartile of each article were performed. RESULTS: The top 50 cited articles were published from 1999-2016, and the total number of citations ranged from 82-602, with 160.36 citations/paper on average. Most of the articles originated from Japan (n = 12), with the most remarkable contributions from Nihon and Okayama Universities, Japan (n = 5, each). The American Journal of Orthodontics and Dentofacial Orthopedics had the most cited articles, with 196.57 citations/paper on average. A significant positive correlation occurred between the number of citations and publication age (rho = 0.392, P = 0.005). CONCLUSION: Our scientometric analysis reported the characteristics of TADs-related articles published over 25 years. Most highly-cited articles were published between 2005 and 2008. The positive correlation between articles' publication date and the number of citations might impact the top 50 within the next 5-10 years.


Subject(s)
Bibliometrics , Humans , Orthodontic Anchorage Procedures/instrumentation , Journal Impact Factor , Periodicals as Topic/statistics & numerical data , Internationality
20.
Sci Rep ; 14(1): 19855, 2024 08 27.
Article in English | MEDLINE | ID: mdl-39191880

ABSTRACT

Soft denture liners have limitations like short lifespan and increased microbial buildup. Despite promise as a non-leaching antimicrobial polymer in dentistry, the impact of dimethylaminododecyl methacrylate (DMADDM) on soft liner performance remains unexplored. This study aimed to evaluate the effect of integrating different concentrations of DMADDM to cold cure acrylic resin soft liner, on its antimicrobial activity, cytotoxicity, and physical properties. The same properties were compared to a conventional commercially available denture soft liner. The study employed a control group (conventional soft liner) and three test groups containing 3.3%, 6.6%, and 10% (total mass fraction) DMADDM, respectively. Antimicrobial activity against Candida albicans and Streptococcus mutans was assessed through colony counts and biofilm biomass. Cytotoxicity was evaluated using an oral epithelial cell line. Additionally, wettability and hardness were measured to assess physical properties. Incorporation of DMADDM significantly reduced Candida albicans and Streptococcus mutans counts, and biofilm biomass, compared to the control. Additionally, DMADDM improved the soft liner's wettability and mitigated long-term hardness increase. In conclusion, DMADDM holds promise in enhancing soft liner performance. However, careful selection of its optimum concentration is crucial to ensure both safety and efficacy for future clinical use.


Subject(s)
Biofilms , Candida albicans , Methacrylates , Streptococcus mutans , Candida albicans/drug effects , Streptococcus mutans/drug effects , Methacrylates/chemistry , Methacrylates/pharmacology , Biofilms/drug effects , Biofilms/growth & development , Humans , Denture Liners , Acrylic Resins/chemistry , Materials Testing , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Dental Materials/pharmacology , Dental Materials/chemistry , Cell Line , Quaternary Ammonium Compounds
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