Preclinical In-Vivo Safety and Toxicokinetics of D-PLEX100 in an Abdominal Surgery Incision Model in Juvenile Miniature Swine.

D-PLEX100 (D-PLEX) is a novel product candidate made of a polymer-lipid-based matrix (PLEX platform) which contains doxycycline that is being released at a constant rate for 30 days. D-PLEX was developed to prevent surgical site infections, which are a major global health challenge. Previous studies have shown its safety in adult humans, adult swine, and adult rabbits. The aim of this study was to assess the toxicity and safety of D-PLEX also in juvenile animals to support future clinical trials in pediatric patients. Yucatan miniature swine were selected as a model, primarily due to their relatively larger mass. D-PLEX or placebo (formulation without doxycycline) was administered locally to abdominal incisions, and the animal's safety parameters were followed for 9 months and compared to sham-control swine. There was no evidence of any systemic safety concern or local toxicity at the incision site in D-PLEX-treated animals. D-PLEX was detected after 1 month and was fully resorbed at the 3-month time point. The surgical incision sites were fully healed at the 6-month time point in all D-PLEX-treated animals. Toxicokinetic (TK) assessments revealed that doxycycline exhibited low Cmax and therefore minimal systemic exposure following a single dose of local administration. This study provides evidence for the safety of D-PLEX and PLEX-based formulation in juvenile miniature swine and supports its further testing in clinical pediatric population. In addition, it can be used as a reference for future preclinical studies aiming to evaluate the safety of other PLEX-based product candidates for the pediatric population.

Efficacy and safety of doxycycline versus iodopovidone for pleurodesis through an intercostal tube in malignant pleural effusions: a randomized trial.

PURPOSE: The search for an inexpensive agent for chemical pleurodesis in malignant pleural effusion (MPE) continues. We aimed to compare the efficacy and safety of iodopovidone versus doxycycline for pleurodesis in MPE. METHODS: We randomized consecutive subjects with recurrent symptomatic MPE (1:1) to undergo pleurodesis with either doxycycline or iodopovidone administered through an intercostal tube. The primary outcome was the success rate of pleurodesis at 30 days. The secondary outcomes were the time to pleurodesis, chest pain (assessed using visual analog scale [VAS]) after pleurodesis, and complications (hypotension, acute respiratory failure, empyema). RESULTS: We randomized 52 and 58 subjects to receive either doxycycline or iodopovidone. The mean (standard deviation [SD]) age of the study population (51% women) was 54.1 (13.6) years. Lung cancer (≥ 60%) was the most common underlying cause of MPE. We observed a similar frequency of success in the doxycycline vs. the iodopovidone group (complete response: 43 (82.7%) vs. 46 (79.3%) subjects; partial response: 7 (13.5%) vs. 10 (17.2%) subjects; p = 0.3). The mean (SD) time to pleurodesis was 1.5 (1.9) days and 1.9 (5.4) days in the doxycycline and iodopovidone groups, respectively. While the VAS for chest pain was significantly higher with iodopovidone (mean [SD] VAS: doxycycline, 31.9 [20.9]; iodopovidone, 41.3 [21.8]; p = 0.017), it did not reach the minimal clinically important difference. The complication rates were similar between the two groups. CONCLUSION: Iodopovidone was not superior to doxycycline for pleurodesis in MPE. TRIAL REGISTRATION NUMBER/DATE: clinicaltrials.gov (NCT02583282) / October 22, 2015.

Tetracycline-, Doxycycline-, Minocycline-Induced Pseudotumor Cerebri and Esophageal Perforation.

Tetracyclines are a class of broad-spectrum bacteriostatic antibiotics used to treat many infections, including methicillin-resistant Staphylococcus aureus (MRSA), acne, pelvic inflammatory disease, chlamydial infections, and a host of zoonotic infections. These drugs work by inhibiting protein synthesis in bacterial ribosomes, specifically by disallowing aminoacyl-tRNA molecules from binding to the ribosomal acceptor sites. While rare, tetracycline antibiotics, particularly minocycline and doxycycline, are associated with an increased risk of developing esophageal perforation and pseudotumor cerebri (PTC, or idiopathic intracranial hypertension). Since tetracyclines are a commonly prescribed class of medications, especially in adolescents for acne treatment, it is important for clinicians to appreciate significant side effects that can result in morbidity and mortality. This paper aims to consolidate and to emphasize current research on the association between tetracycline antibiotics and the development of esophageal perforation, and PTC. PTC is a neurological syndrome consisting of increased intracranial pressure, headache, and vision changes without evidence of the contributing source, such as mass lesion, infection, stroke, or malignancy. Esophageal perforation, while rare, can be the result of pill esophagitis. Pill-induced injuries occur when caustic medicinal pills dissolve in the esophagus rather than in the stomach. Most patients experience only self-limited pain (retrosternal burning discomfort, heartburn, dysphagia, or odynophagia), but hemorrhage, stricture, and perforation may occur. Tetracycline use can lead to pill esophagitis. In summary, clinicians should appreciate the potential risks of tetracycline compounds in clinical practice.

Doxycycline hyclate may damage testicular germinal epithelium in Wistar rats

Broad-spectrum antimicrobial doxycycline acts as an inhibitor of protein synthesis and it is widely used in the clinical treatment of various infections by microorganisms that are sensitive to the drug, as well as in animal feed. Its liposolubility guarantees its high tissue bioavailability, being associated with several biochemical changes in the organism and potentially adverse effects on reproduction. This study aims to evaluate the effects of the action of doxycycline on spermatogenesis to provide a complete analysis of the tubular and interstitial compartments and to identify possible changes in the testicular parenchyma. Adult male Wistar rats were divided into three groups: one control (water), and two treated with doxycycline at the doses of 10mg/kg and 30mg/kg, for 30 days. After euthanasia and sample processing, the following parameters were evaluated: a) tubular diameter and height of the seminiferous epithelium; b) volumetric proportions (%) and volumes (mL) of the components of the testicular parenchyma; c) counting testicular germ cell populations; d) evaluation of cell viability. The results of the comparative evaluation between the experimental groups demonstrated a significant increase in the diameter and area of the tubular lumen and a reduction in the count of spermatogonia in the experimental group that received doxycycline hyclate at a dose of 30mg/kg. In the same experimental group, an increase in the overall yield of spermatogenesis was found as a consequence of the increase in the mitotic index.

Ocular Rosacea microBiome Study (ORBS)-sub-microbial versus antibiotic dosing of doxycycline versus placebo in treatment of symptomatic ocular rosacea: study protocol for a parallel-arm randomized clinical trial.

BACKGROUND: Ocular rosacea is common and is often managed with long-term antibiotic treatment. Doxycycline is the most commonly selected antibiotic for the treatment of rosacea. As there is no established standard of care treatment dose for rosacea, prescribed doses of doxycycline vary widely. The FDA classifies 40 mg daily dose of doxycycline for ocular rosacea as sub-microbial in comparison to an antibiotic dose of 200 mg daily. However, this "sub-microbial" dose has never been evaluated in patients with ocular rosacea, and even the sub-microbial dose has potential to alter systemic mucosa flora. Here, we present a randomized controlled trial using RNA sequencing to fully characterize the impact of sub-microbial antibiotic dosing of doxycycline on antimicrobial resistance and bacterial composition of the ocular and gut flora. METHODS: In a triple-masked parallel randomized control trial, patients with ocular rosacea will be randomized to three arms: a 40-mg dose of doxycycline, a 200-mg antibiotic dose of doxycycline, or placebo. Collected rectal and lower eyelid samples will be compared for frequency of antimicrobial resistance genetic determinants and microbiome diversity. A subjective ocular surface disease index survey and objective tear breakup time measurement will be determined. DISCUSSION: These results will enhance our understanding of the overall systemic impact of long-term systemic sub-microbial antibiotic dosing for the treatment of chronic recurrent ocular inflammatory diseases. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.org (NCT05296837) on March 22, 2022.

Biopsy Confirmed Doxycycline Induced Gastric Mucosal Injury.

Doxycycline (DOX) is a tetracycline antibiotic that is prescribed for treating a variety of infections involving the skin, respiratory tract, and urogenital system. Adversely, esophageal mucosal injury due to DOX is well described; however, gastric mucosal injury is less commonly reported and may result in severe gastrointestinal hemorrhage and occasionally, perforation. In most reported cases of DOX-induced gastric lesions, patients are symptomatic upon presentation leading to endoscopic evaluation and diagnosis with biopsy. However, severe gastric insults may go unrecognized in rare cases of asymptomatic patients, increasing the risk of mortality.

A phase 2 study for evaluating doxycycline 50 mg once daily and 100 mg once daily as preemptive treatment for skin toxicity in patients with metastatic colorectal cancer treated with an anti-EGFR and chemotherapy.

PURPOSE: To assess the efficacy, safety, and quality-of-life outcomes of doxycycline 50 or 100 mg once daily in the prevention of skin toxicity in patients undergoing chemotherapy plus anti-EGFR therapy as first-line treatment of metastatic colorectal cancer (mCRC). METHODS: Phase II, multicenter, single-arm, exploratory study was conducted in 7 Spanish hospitals. The primary study outcome was the incidence of ≥ grade 2 skin toxicities during the 6-week skin treatment period. Quality of life was assessed with the Dermatology Life Quality Index (DLQI) questionnaire. Patients had to receive either doxycycline 50 mg once daily in a first stage with 10 patients, or, if more than three patients presented ≥ grade 2 skin toxicities, the next 30 patients had to receive 100 mg once daily. RESULTS: Thirty-four patients with RAS wild-type mCRC were enrolled in the study. Ten patients were first treated with doxycycline 50 mg once daily, and the following 24 were treated with doxycycline 100 mg once daily. A total of 60.0% (95% CI 29.6-90.0) and 20.8% (95% CI 4.6-37.0) of patients who received doxycycline 50 mg/day and 100 mg/day, respectively, had at least one ≥ grade 2 skin toxicity. Patients treated with doxycycline 100 mg once daily experienced less QoL deterioration. Only 1 patient reported a mild doxycycline-related gastrointestinal adverse event. CONCLUSION: Our results suggest that doxycycline doses as low as 100 mg once daily are efficacious and well tolerated for the prevention of skin toxicity in patients with mCRC who undergo treatment with chemotherapy plus EGFR-targeted therapies. TRIAL REGISTRATION: ClinicalTrials.gov NCT03448731.

Chemotherapeutics Combined with Luminal Irritants: Effects on Small-Intestinal Mannitol Permeability and Villus Length in Rats.

Chemotherapy causes intestinal mucositis, which includes villous atrophy and altered mucosal barrier function. However, there is an uncertainty regarding how the reduced small-intestinal surface area affects the mucosal permeability of the small marker probe mannitol (MW 188), and how the mucosa responds to luminal irritants after chemotherapy. The aims in this study were to determine (i) the relationship between chemotherapy-induced villus atrophy and the intestinal permeability of mannitol and (ii) how the mucosa regulate this permeability in response to luminal ethanol and sodium dodecyl sulfate (SDS). This was investigated by treating rats with a single intraperitoneal dose of doxorubicin, irinotecan, or 5-fluorouracil. After 72 h, jejunum was single-pass perfused and mannitol permeability determined at baseline and after 15 min luminal exposure to 15% ethanol or 5 mg/mL SDS. Tissue samples for morphological analyses were sampled from the perfused segment. All three chemotherapeutics caused a similar 30% reduction in villus length. Mannitol permeability increased with irinotecan (1.3-fold) and 5-fluorouracil (2.5-fold) and was reduced with doxorubicin (0.5-fold), suggesting that it is not epithelial surface area alone that regulates intestinal permeability to mannitol. There was no additional increase in mannitol permeability induced by luminal ethanol or SDS in the chemotherapy-treated rats compared to controls, which may be related to the relatively high basal permeability of mannitol compared to other common low-permeability probes. We therefore suggest that future studies should focus on elucidating the complex interplay between chemotherapy in combination with luminal irritants on the intestinal permeability of other probes.

Data mining for detecting signals of adverse drug reaction of doxycycline using the Korea adverse event reporting system database.

BACKGROUND: Doxycycline is one of the most prescribed antibiotics by dermatologists. However, the concern regarding adverse events of doxycyline has been rising. OBJECTIVE: To detect the adverse events of doxycycline using the Korea Adverse Events Reporting System (KAERS) database from January 2014 to December 2018 through a data mining method. METHODS: A signal was defined as one satisfying all three indices; a proportional reporting ratio, a reporting odds ratio, and an information component. We further checked whether the detected signals exist in drug labels in Korea and five developed countries, the United States, the United Kingdom, Germany, Canada, and Japan. RESULTS: A total of 3,365,186 adverse event-drug pairs were reported and of which 3,075 were associated with doxycycline. Among the thirty-seven signals, nineteen (malaise, ileus, confusion, malignant neoplasm, ectopic pregnancy, ovarian hyperstimulation, vaginal hemorrhage, bone necrosis, acne, rosacea, seborrheic dermatitis, folliculitis, skin ulceration, crusting, dry skin, paronychia, mottled skin, application site reaction, and application site edema) were not included on any of the drug labels of the six countries. CONCLUSION: We identified nineteen new doxycycline signals that did not appear on drug labels in six countries. Further studies are warranted to evaluate the causality of the adverse events with doxycycline.

Treatment of rosacea during pregnancy.

BACKGROUND: Exacerbation of rosacea may occur during pregnancy and there are multiple associated cases of rosacea fulminans (RF). Treatment during pregnancy poses a significant challenge as many rosacea treatments are contraindicated or have limited evidence regarding potential adverse fetal effects. OBJECTIVE: Review the pregnancy categories of various treatments and develop algorithms for treating pregnant patients with rosacea and RF. METHODS: Rosacea treatments showing efficacy in randomized controlled trials were searched through DailyMed to review pregnancy labelling. Searching the PubMed/MEDLINE database for English articles using keywords "rosacea fulminans AND pregnancy" without publishing-time restrictions yielded 8 articles. We summarized treatments used in cases of RF during pregnancy. RESULTS: Topical ivermectin was more effective than metronidazole, but has a more concerning pregnancy category. Three pregnant women with RF were treated successfully with topical metronidazole in combination with other therapies. Azithromycin is the only oral rosacea therapy that is considered safe for pregnant patients and it has been used to treat RF. CONCLUSIONS: This review highlights the challenging aspects of treating pregnant patients with rosacea, as there is limited pregnancy-related treatment efficacy and safety data. The pregnancy categories of therapeutic options are summarized. Further studies are needed to learn which therapies are effective and safe for use during pregnancy.

Oral antibiotics for chronic blepharitis.

BACKGROUND: Posterior blepharitis is common and causes ocular surface and lid damage as well as discomfort. It affects 37% to 47% of all ophthalmology patients; its incidence increasing with age. It is a multifactorial disease associated with multiple other pathologies, such as rosacea, meibomianitis, and infections. Treatment usually focuses on reliefing the symptoms by using artificial tears, lid scrubs, and warm compresses. The condition may be notoriously difficult to manage adequately once it becomes chronic. One such management approach for chronic blepharitis is the use of oral antibiotics for both their antibacterial as well as anti-inflammatory properties. There are currently no guidelines regarding the use of oral antibiotics, including antibiotic type, dosage, and treatment duration, for the treatment of chronic blepharitis. OBJECTIVES: To assess the benefits and harms of oral antibiotic use for people with chronic blepharitis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2020, Issue 8); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 29 August 2020. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing oral antibiotics with placebo in adult participants with chronic blepharitis (including staphylococcal, seborrhoeic, or Meibomian Gland Dysfunction (MGD)). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology and graded the certainty of the body of evidence for six outcomes using the GRADE classification. MAIN RESULTS: We included two studies with 220 participants (numbers of eyes unclear). One parallel-group RCT comparing oral doxycycline (40 mg once a day) with placebo enrolled 70 participants with blepharitis and facial rosacea in the USA. Follow-up duration was three months. One three-arm RCT conducted in South Korea investigated the effect of high-dose (200 mg twice a day) and low-dose (20 mg twice a day) doxycycline versus placebo after one month of study medication. It enrolled 50 participants with chronic MGD in each study arm (i.e. 150 participants enrolled in total). The two studies did not evaluate the same outcome measurements, which precluded any meta-analysis. The evidence for the effect of oral antibiotics on subjective improvement in symptoms was very uncertain. One study suggested that there was little to no effect of oral doxycycline on subjective symptoms based on the Ocular Surface Disease Index (OSDI) scores ranging from 0 to 100 (higher score indicates worse condition) (mean difference (MD) 3.55, 95% confidence interval (CI) -4.61 to 11.71; n = 70) and bulbar conjunctival hyperemia ranging from 0 (clear) to 4 (severe) (MD -0.01, 95% CI -0.38 to 0.36; n = 70) at 12 weeks. The three-arm RCT showed that oral doxycycline may slightly improve number of symptoms (MD -0.56, 95% CI -0.95 to -0.17; n = 93 (high-dose doxycycline versus placebo); MD -0.48, 95% CI -0.86 to -0.10; n = 93 (low-dose doxycycline versus placebo)) and proportion of participants with symptom improvement (risk ratio (RR) 6.13, 95% CI 2.61 to 14.42; n = 93 (high-dose doxycycline versus placebo); RR 6.54, 95% CI 2.79 to 15.30; n = 93 (low-dose doxycycline versus placebo)) at one month, but the evidence is very uncertain. We judged the certainty of evidence for subjective symptoms as very low. One study evaluated aqueous tear production by Schirmer's test (mm/5 min) (higher score indicates better condition) and tear film stability by measuring tear film break-up time (TBUT) in seconds (higher score indicates better condition) at one month. We found very low certainty evidence that oral doxycycline may improve these clinical signs. The estimated MD in Schirmer's test score after one month of treatment was 4.09 mm (95% CI 2.38 to 5.80; n = 93) in the high-dose doxycycline group versus the placebo group and 3.76 mm (95% CI 1.85 to 5.67; n = 93) in the low-dose doxycycline group versus the placebo group. The estimated MD in TBUT after one month was 1.58 seconds (95% CI 0.57 to 2.59; n = 93) when comparing the high-dose doxycycline group with the placebo group, and 1.70 seconds (95% CI 0.96 to 2.44; n = 93) when comparing the low-dose doxycycline group with the placebo group. Although there was a noted improvement in these scores, their clinical importance remains uncertain. One study suggested that oral doxycycline may increase the incidence of serious side effects: 18 (39%) participants in the high-dose doxycycline group, 8 (17%) in the low-dose doxycycline group, and 3 (6%) out of 47 participants in the placebo group experienced serious side effects (RR 6.13, 95% CI 1.94 to 19.41; n = 93 (high-dose doxycycline versus placebo); RR 2.72, 95% CI 0.77 to 9.64; n = 93 (low-dose doxycycline versus placebo)). Additionally, one study reported that one case of migraine headache and five cases of headache were observed in the oral doxycycline group, and one case of non-Hodgkin's lymphoma was observed in the placebo group. We judged the certainty of evidence for adverse events as very low. AUTHORS' CONCLUSIONS: There was insufficient evidence to draw any meaningful conclusions on the use of oral antibiotics for chronic blepharitis. Very low certainty evidence suggests that oral antibiotics may improve clinical signs, but may cause more adverse events. The evidence for the effect of oral antibiotics on subjective symptoms is very uncertain. Further trials are needed to provide high quality evidence on the use of oral antibiotics in the treatment of chronic blepharitis.

Ulceración esofágica por ingestión de doxiciclina / Doxycycline induced esophageal ulceration

La ulceración esofágica por ingestión de doxiciclina es una de las causas más frecuentes de lesión esofágica. Ha sido subdiagnosticada y escasamente reconocida en dermatología. El dolor retroesternal, la odinofagia de aparición brusca y el antecedente de ingesta de doxiciclina u otros fármacos son características que facilitan su diagnóstico. Puede presentar complicaciones serias, como hemorragias, estenosis y mediastinitis.

Esophageal ulceration due to ingestion of doxycycline is one of the most frequent causes of esophageal injury. It has been underdiagnosed and scarcely recognized in dermatology. Retrosternal pain, sudden odynophagia and a history of doxycycline or other drugs intake are some of the characteristics that lead to diagnosis. It may cause severe complications such as bleeding, stenosis and mediastinitis.

Effect of Antimicrobial Therapy on Respiratory Hospitalization or Death in Adults With Idiopathic Pulmonary Fibrosis: The CleanUP-IPF Randomized Clinical Trial.

Importance: Alteration in lung microbes is associated with disease progression in idiopathic pulmonary fibrosis. Objective: To assess the effect of antimicrobial therapy on clinical outcomes. Design, Setting, and Participants: Pragmatic, randomized, unblinded clinical trial conducted across 35 US sites. A total of 513 patients older than 40 years were randomized from August 2017 to June 2019 (final follow-up was January 2020). Interventions: Patients were randomized in a 1:1 allocation ratio to receive antimicrobials (n = 254) or usual care alone (n = 259). Antimicrobials included co-trimoxazole (trimethoprim 160 mg/sulfamethoxazole 800 mg twice daily plus folic acid 5 mg daily, n = 128) or doxycycline (100 mg once daily if body weight <50 kg or 100 mg twice daily if ≥50 kg, n = 126). No placebo was administered in the usual care alone group. Main Outcomes and Measures: The primary end point was time to first nonelective respiratory hospitalization or all-cause mortality. Results: Among the 513 patients who were randomized (mean age, 71 years; 23.6% women), all (100%) were included in the analysis. The study was terminated for futility on December 18, 2019. After a mean follow-up time of 13.1 months (median, 12.7 months), a total of 108 primary end point events occurred: 52 events (20.4 events per 100 patient-years [95% CI, 14.8-25.9]) in the usual care plus antimicrobial therapy group and 56 events (18.4 events per 100 patient-years [95% CI, 13.2-23.6]) in the usual care group, with no significant difference between groups (adjusted HR, 1.04 [95% CI, 0.71-1.53; P = .83]. There was no statistically significant interaction between the effect of the prespecified antimicrobial agent (co-trimoxazole vs doxycycline) on the primary end point (adjusted HR, 1.15 [95% CI 0.68-1.95] in the co-trimoxazole group vs 0.82 [95% CI, 0.46-1.47] in the doxycycline group; P = .66). Serious adverse events occurring at 5% or greater among those treated with usual care plus antimicrobials vs usual care alone included respiratory events (16.5% vs 10.0%) and infections (2.8% vs 6.6%); adverse events of special interest included diarrhea (10.2% vs 3.1%) and rash (6.7% vs 0%). Conclusions and Relevance: Among adults with idiopathic pulmonary fibrosis, the addition of co-trimoxazole or doxycycline to usual care, compared with usual care alone, did not significantly improve time to nonelective respiratory hospitalization or death. These findings do not support treatment with these antibiotics for the underlying disease. Trial Registration: ClinicalTrials.gov Identifier: NCT02759120.

A Rare Laryngeal Presentation of Stevens-Johnson Syndrome.

Stevens-Johnson syndrome (SJS) is a rare but severe mucocutaneous epidermolysis commonly triggered by medications. SJS is characterized by mucocutaneous lesions of the trunk, face, and limbs, as well as the oral cavity, gastrointestinal tract, and respiratory tract. Although uncommon, laryngeal involvement in SJS can lead to severe respiratory, phonatory and deglutitive complications. Providers caring for patients with SJS should maintain a high index of suspicion for laryngeal involvement and low threshold to solicit Otolaryngology consultation. Laryngeal complications can be more expediently managed when anticipated early in the course of disease. Laryngoscope, 131:2519-2522, 2021.

Doxycycline aggravates granulomatous inflammation and lung microstructural remodeling induced by Schistosoma mansoni infection.

Although doxycycline exhibits immunomodulatory properties, its effects on pulmonary infection by Schistosoma mansoni remain overlooked. Thus, we investigated the impact of this drug on lung granulomatous inflammation and microstructural remodeling in a murine model of schistosomiasis. Swiss mice were randomized in four groups: (i) uninfected, (ii) infected with S. mansoni and untreated, (iii) infected treated with praziquantel (Pzq; 200 mg/kg), and (iv) infected treated with Dox (50 mg/kg). Pz was administered in a single dose, and Dox for 60 days. S. mansoni induced marked granulomatous lung inflammation, which was associated to cytokines upregulation (IL-2, IL-4, IL-10, IFN-γ, TNF-α, and TGF-ß), neutrophils and macrophages recruitment, alveolar collapse, lung fibrosis, and extensive depletion of elastic fibers. These parameters were attenuated by Pzq and aggravated by Dox. Exudative/productive granulomas were predominant in untreated and Dox-treated animals, while fibrotic granulomas were more frequent in Pzq-treated mice. The number and size of granulomas in Dox-treated animals was higher than untreated and Pzq-treated mice. Dox treatment inhibited the increase in MMP-1 and MMP-2 activity but upregulated myeloperoxidase and N-acetylglucosaminidase activity compared to untreated and Pzq-treated animals. Dox and Pzq exerted no effect on elastin depletion and upregulation of elastase activity. Together, our findings indicated that Dox aggravated granulomatous inflammation, accelerating lung microstructural remodeling by downregulating MMP-1 and MMP-2 activity without impair neutrophils and macrophages recruitment or elastase activity. Thus, Dox potentiates inflammatory damage associated with lung fibrosis, elastin depletion and massive alveolar collapse, profoundly subverting lung structure in S. mansoni-infected mice.

Doxycycline-induced idiopathic intracranial hypertension in a patient with Lyme disease.

ABSTRACT: Doxycycline is widely used to treat early and disseminated Lyme disease. Idiopathic intracranial hypertension (IIH), also known as pseudotumor cerebri, is a rare but serious adverse reaction to this medication. This article reviews the pathophysiology, presentation, diagnosis, and treatment of a patient with disseminated Lyme disease complicated by doxycycline-induced IIH.