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Cureus May 2024Pemphigus vulgaris (PV) stands as a rare autoimmune disorder characterized by blistering and erosion of mucocutaneous membranes. The pathogenesis of PV implicates both B...
Pemphigus vulgaris (PV) stands as a rare autoimmune disorder characterized by blistering and erosion of mucocutaneous membranes. The pathogenesis of PV implicates both B and T cells, which target cell-to-cell adhesion molecules within the epithelia of the skin and oral mucosa, leading to acantholysis. Typically, the presentation involves blistering of the oral mucosa, often followed by cutaneous lesions. Given the considerable risk of morbidity and mortality associated with PV, early diagnosis is crucial, typically relying on a combination of clinical features, histopathology, and direct immunofluorescence. Bruton tyrosine kinase (BTK) plays a significant role in the pathophysiology of autoimmune diseases and inflammation. Herein, we present a case of PV that demonstrated resistance to first-line therapy with steroids. Subsequently, treatment with the BTK inhibitor ibrutinib was initiated, yielding favorable outcomes. This case underscores the potential of targeted therapies, such as BTK inhibitors, in managing PV refractory to conventional treatment modalities.
PubMed: 38947690
DOI: 10.7759/cureus.61317 -
Veterinary and Animal Science Sep 2024Previously, we demonstrated unique insertion/deletion polymorphisms of equine histidine-rich glycoprotein with five genotypes composed of 45-bp or 90-bp deletions in...
Previously, we demonstrated unique insertion/deletion polymorphisms of equine histidine-rich glycoprotein with five genotypes composed of 45-bp or 90-bp deletions in the histidine-rich region of in Thoroughbred horses. Although leukocytes are typically used to collect DNA for genotyping, blood sampling from animals is sometimes difficult and invasive. Moreover, the method for extracting DNA from blood leukocytes involves complicated steps and must be performed soon after blood sampling for sensitive gene analysis. In the present study, we performed genotyping using DNA, isolated from oral mucosa swabs collected by rubbing the mucosa on the underside of the upper lip of horses and 100 mg of freshly excreted feces obtained by scraping their surface. In the present study, we performed genotyping using DNA isolated from oral mucosa swabs and feces of horses (18 Thoroughbreds, 17 mixed breeds, 2 warm bloods), and compared the accuracy of this method with that of the method using DNA from leukocytes. The DNA derived from oral mucosa swabs was sufficient in quantity and quality for genotyping. However, DNA derived from fecal samples requires a more sensitive detection system because of contamination with non-horse DNA, and the test quality is low. Collection of oral mucosa swabs is less invasive than blood sampling; further, oral swabs can be stored for a longer period in a specified high-quality solution. Therefore, collecting DNA samples from oral mucosa swabs is recommended for the genetic analysis of not only horses but also other animals that are not accustomed to humans.
PubMed: 38947185
DOI: 10.1016/j.vas.2024.100361 -
Yakugaku Zasshi : Journal of the... 2024It is well known that the oral bioavailability of hydrophilic and macromolecular drugs is generally very poor due to their poor membrane permeability characteristics.... (Review)
Review
It is well known that the oral bioavailability of hydrophilic and macromolecular drugs is generally very poor due to their poor membrane permeability characteristics. Among these poorly absorbed drugs, peptide and protein drugs are typical poorly absorbed drugs which have low stability and poor permeability in the gastrointestinal tract. Consequently, the clinical administration of peptide and protein drugs is presently limited to administration by injection. However, such frequent administration subjects the patients to considerable pain, and there is also the possibility of the manifestation of serious side effects. Therefore, various approaches have been examined to overcome the poor absorption characteristics of these drugs. These approaches include (1) to use additives including absorption enhancers and protease inhibitors, (2) to modify the chemical structure of peptide and protein drugs, and (3) to apply dosage forms to these drugs, (4) to develop a novel administration method for these drugs that can serve as an alternative to oral and injection administration. We demonstrated that intestinal and transmucosal absorption of peptide and protein drugs could be improved by using these approaches. These approaches may give us useful basic information to improve the intestinal and transmucosal absorption of peptide and protein drugs.
Topics: Humans; Intestinal Absorption; Peptides; Proteins; Biological Availability; Protease Inhibitors; Permeability; Administration, Oral; Intestinal Mucosa; Dosage Forms
PubMed: 38945845
DOI: 10.1248/yakushi.23-00199 -
Pathology, Research and Practice Jun 2024Oral Submucous Fibrosis (OSMF) is a chronic precancerous disorder of the oral mucosa caused by chewing of areca nut and its other variants. Chewing of areca nuts leads...
Oral Submucous Fibrosis (OSMF) is a chronic precancerous disorder of the oral mucosa caused by chewing of areca nut and its other variants. Chewing of areca nuts leads to dysregulated expression of specific genes, leading to various premalignant or malignant disorders. This study aimed to determine the differential expression of the diagnostic genes (MYH6, TNNT3, MYL1, and TPM2) in healthy controls and OSMF patients using saliva and tissue samples, determining the histopathological grade of the clinical samples. A total of 20 patients were included in the study and were divided into two groups: Group I consisted of 10 healthy patients (control group) and Group II consisted of 10 OSMF patients. Unstimulated whole saliva samples were collected from both groups, and the tissue samples were divided into two parts: one for RT-qPCR analysis and the other for histopathological assay. The expression profile of genes concerning OSMF saliva and tissue samples was significantly upregulated compared to the healthy control, and all the clinical samples of the study were categorized into histopathological grade 1. The findings of this study concluded that these genes can be referred to as diagnostic genes for OSMF in early and very early clinical samples, and saliva can be used as a promising diagnostic tool for early OSMF studies.
PubMed: 38944023
DOI: 10.1016/j.prp.2024.155416 -
Oral Oncology Jun 2024To assess the prognostic importance of margin in resected buccal cancer within a framework of risk factor-driven postoperative adjuvant treatment.
OBJECTIVE
To assess the prognostic importance of margin in resected buccal cancer within a framework of risk factor-driven postoperative adjuvant treatment.
MATERIALS AND METHODS
Consecutive, treatment naïve patients undergoing primary surgical treatment for buccal cancer. Margin was defined as clear (≥5 mm), close (1-4 mm) and involved (<1 mm). Main outcome was association of margin with local recurrence free survival (LRFS). Subgroup analysis of close margin was performed according to receipt or no receipt of adjuvant treatment. A numerical margin cut-off in mm that could independently predict LRFS was sought to be identified.
RESULTS
Of the 167 patients included, the frequency of clear, close and involved margins was 50 (30 %), 78 (47 %) and 39 (23 %) respectively, among whom 52 %, 44 % and 98 % received postoperative adjuvant treatment respectively. Clear and close margins had similar 3-year LRFS (89 % and 96 % respectively), while involved margin had worse 3-year LRFS at 65 %. Involved margin was confirmed to be strongly and independently associated with worse LRFS. Within close margin, receipt and no receipt of adjuvant treatment had similar 3-year LRFS (92 % and 100 % respectively). A margin cut-off of 2 mm was identified at or above which LRFS approximated that of clear margin.
CONCLUSIONS
This single center cohort study of patients with resected buccal cancer suggests that close margin is distinct from and has a better LRFS than involved margin. A subset of close margin, with margin size ≥ 2 mm and no other adverse features, might be spared adjuvant treatment without compromising outcomes.
PubMed: 38943869
DOI: 10.1016/j.oraloncology.2024.106927 -
Scientific Reports Jun 2024The tobacco alkaloid nicotine is known for its activation of neuronal nicotinic acetylcholine receptors. Nicotine is consumed in different ways such as through...
The tobacco alkaloid nicotine is known for its activation of neuronal nicotinic acetylcholine receptors. Nicotine is consumed in different ways such as through conventional smoking, e-cigarettes, snuff or nicotine pouches. The use of snuff has been associated with several adverse health effects, such as inflammatory reactions of the oral mucosa and oral cavity cancer. We performed a metabolomic analysis of nicotine-exposed THP-1 human monocytes. Cells were exposed to 5 mM of the alkaloid for up to 4 h, and cell extracts and medium subjected to untargeted liquid chromatography high-resolution mass spectrometry. Raw data processing revealed 17 nicotine biotransformation products. Among these, cotinine and nornicotine were identified as the two major cellular biotransformation products. The application of multi- and univariate statistical analyses resulted in the annotation, up to a certain level of identification, of 12 compounds in the cell extracts and 13 compounds in the medium that were altered by nicotine exposure. Of these, four were verified as methylthioadenosine, cytosine, uric acid, and L-glutamate. Methylthioadenosine levels were affected in both cells and the medium, while cytosine, uric acid, and L-glutamate levels were affected in the medium only. The effects of smoking on the pathways involving these metabolites have been previously demonstrated in humans. Most of the other discriminating compounds, which were merely tentatively or not fully identified, were amino acids or amino acid derivatives. In conclusion, our preliminary data suggest that some of the potentially adverse effects related to smoking may also be expected when nicotine is consumed via snuff or nicotine pouches.
Topics: Humans; Nicotine; Metabolomics; Monocytes; Mass Spectrometry; THP-1 Cells; Cotinine; Chromatography, Liquid; Metabolome; Glutamic Acid
PubMed: 38942832
DOI: 10.1038/s41598-024-65733-7 -
Bioorganic Chemistry Jun 2024Aiming to discover effective and safe non-steroidal anti-inflammatory agents, a new set of 1,2,4-triazole tetrahydroisoquinoline hybrids 9a-g, 11a-g and 12a-g was...
Aiming to discover effective and safe non-steroidal anti-inflammatory agents, a new set of 1,2,4-triazole tetrahydroisoquinoline hybrids 9a-g, 11a-g and 12a-g was synthesized and evaluated as inhibitors of COX-1 and COX-2. In order to overcome the adverse effects of highly selective COX-2 and non-selective COX-2 inhibitors, the compounds of this study were designed with the goal of obtaining moderately selective COX-2 inhibitors. In this study compounds 9e, 9g and 11f are the most effective derivatives against COX-2 with IC values 0.87, 1.27 and 0.58 µM, respectively which are better than or comparable to the standard drug celecoxib (IC = 0.82 µM) but with lower selectivity indices as required by our goal design. The results of the in vivo anti-inflammatory inhibition test revealed that compounds 9e, 9g and 11f displayed a higher significant anti-inflammatory activity than celecoxib at all-time intervals. In addition, these compounds significantly decreased the production of inflammatory mediators PGE-2, TNF-ɑ and IL-6. Compounds 9e, 9g and 11f had a safe gastric profile compared to indomethacin, also compound 11f (ulcerogenic index = 1.33) was less ulcerous than the safe celecoxib (ulcerogenic index = 3). Moreover, histopathological investigations revealed a normal architecture of both paw skin and gastric mucosa after oral treatment of rats with compound 11f. Furthermore, molecular docking studies were performed on COX-1 and COX-2 to study the binding pattern of compounds 9e, 9g and 11f on both isoenzymes.
PubMed: 38941697
DOI: 10.1016/j.bioorg.2024.107577 -
Clinical Oral Investigations Jun 2024The purpose of this prospective cohort study is to evaluate the effect of peri-implant phenotype (PPh) on the severity of peri-implant diseases and the results of...
OBJECTIVES
The purpose of this prospective cohort study is to evaluate the effect of peri-implant phenotype (PPh) on the severity of peri-implant diseases and the results of non-surgical mechanical treatment (NSMT), along with calprotectin (CLP) and MMP-8(matrix metalloproteinase-8) levels.
MATERIALS AND METHODS
77 implants from 39 patients were included. The implants were categorized Group-1(peri-implant mucositis), Group-2(peri-implantitis).Baseline (0. Month-PrT) clinical parameters (PD, GI, PI, BOP, CAL) and radiographic bone loss were documented, and peri-implant crevicular fluid (PICF) samples were collected. Various intruments and methodologies were employed to assess PPh components (mucosa thickness, supracrestal tissue height, keratinized mucosa) and peri-implant attached mucosa (AM). NSMT was applied to diseased implant sites. All clinical parameters were reassessed again by taking PICF samples at the 6th month-after treatment (PT). In PICF samples obtained from both groups, MMP-8 and CLP levels were evaluated using the ELISA test.
RESULTS
PrT-PD,PrT-GI,PrT-CAL and PrT-BOP percentage values in Group-2 were significantly higher than Group-1.PrT-PD,PrTPI scores are significantly higher in thin biotype implants. All components of the PPh and AM were significantly lower in thin biotype. Intra-group time-dependent changes of MMP-8 and CLP were significant in both groups (p < 0.05). When the relationship between thin and thick biotype and biochemical parameters was evaluated, the change in PrT-PT didn't show a significant difference (p > 0.05).
CONCLUSIONS
PPh plays a role in influencing the severity of peri-implant diseases. However, the impact of phenotype on NSMT outcomes was similar in both groups.
CLINICAL RELEVANCE
The PPh should be considered when planning implant surgery.
Topics: Humans; Matrix Metalloproteinase 8; Female; Prospective Studies; Peri-Implantitis; Male; Middle Aged; Phenotype; Gingival Crevicular Fluid; Leukocyte L1 Antigen Complex; Dental Implants; Enzyme-Linked Immunosorbent Assay; Biomarkers; Stomatitis; Periodontal Index; Adult; Aged
PubMed: 38940878
DOI: 10.1007/s00784-024-05798-w -
Journal of the Korean Association of... Jun 2024This prospective observational study aimed to assess the clinical outcomes of perioperative airway and ventilatory management in patients undergoing surgery for oral...
OBJECTIVES
This prospective observational study aimed to assess the clinical outcomes of perioperative airway and ventilatory management in patients undergoing surgery for oral cavity cancer. The study described the frequencies and types of procedures for securing the airway and the duration and types of postoperative ventilatory support. We compared the findings with those of the TRACHY study.
PATIENTS AND METHODS
One hundred patients undergoing oral cavity oncological surgeries were included. Airway assessment included inter-incisor gap, Mallampati class, neck movements, and radiological features. Surgical parameters, postoperative ventilatory support, and complications were documented.
RESULTS
The buccal mucosa was the most common cancer site (48.0%), and direct laryngoscopy was deemed difficult in 58.0% of patients. Awake fibreoptic intubation or elective tracheostomy was required in 43.0% of cases. Thirty-three patients were extubated on the table, and 34 patients were successfully managed with a delayed extubation strategy. In comparison with the TRACHY study, variations were observed in demographic parameters, tumour characteristics, and surgical interventions. Our mean TRACHY score was 1.38, and only five patients had a score ≥4. Prophylactic tracheostomy was performed in 2.0% of cases, in contrast to the TRACHY study in which 42.0% of patients underwent the procedure.
CONCLUSION
The study emphasizes the challenges in airway management for oral cavity cancer surgery. While prophylactic tracheostomy may be necessary in specific cases, individualized approaches, including delayed extubation, are preferrable to maximize safety. Our findings contribute to better understanding and managing perioperative challenges in oral cancer patients and highlight the need for personalized strategies. Scoring systems like TRACHY should not be accepted as universally applicable.
PubMed: 38940651
DOI: 10.5125/jkaoms.2024.50.3.146 -
Case Reports in Otolaryngology 2024Cocaine is the second most consumed drug worldwide, more than 0.4% of the global population, and has become a real public health problem in recent years. Its inhalation...
BACKGROUND
Cocaine is the second most consumed drug worldwide, more than 0.4% of the global population, and has become a real public health problem in recent years. Its inhalation causes significant centrofacial lesions, grouped under the name cocaine-induced midline destructive lesion (CIMDL). These destructions are due to the conjunction of the vasoconstrictor, local prothrombogenic effects, and cytotoxic effects of cocaine. The ischemia produced by this substance is due to vasoconstriction that leads to nasal tissue necrosis and perforation of the nasal septum secondary to chondral necrosis. . A 36-year-old man, previously grappling with cocaine addiction, was hospitalized to undergo comprehensive clinical, microbiological, and radiological examinations because he was suffering from the emergence of crusts and ulceration in the nasal mucosa, accompanied by a palate perforation, a 39°C fever, and chills. Standard bacteriological culture was positive for coagulase-negative staphylococci and , while mycological culture was positive for . The CT scan images of the sinuses confirmed the presence of palatal perforation and total destruction of the nasal septum, cartilaginous portion, maxillary sinus medial wall, lower and middle turbinates, and middle meatus. Nasal endoscopy revealed an exposition of the bony wall and displayed the exposition of the occipital bone's clivus. A diagnosis of CIMDL was confirmed. Antibiotic therapy was decided based on antibiogram results by the consulting microbiologist. Debridement of necrotic tissue was done by nasal endoscopy with local cleaning and was repetitive during the first week to maintain the best cleanliness possible. The patient was discharged with oro-nasal hygiene instructions and referred for prosthetic rehabilation. As for the cocaine addiction, the patient was in follow-up with a psychologist in a specialized centre.
CONCLUSION
The care is multidisciplinary. Psychological help and assistance are essential to guide patients to become cocaine free and to avoid a relapse. Weaning is a prerequisite for surgery. Rehabilitation of speech and swallowing is necessary. Many local flaps or micro-anastomoses are possible.
PubMed: 38939732
DOI: 10.1155/2024/7109261