Broad-spectrum Tetracycline Research Articles

Doxycycline pharmacokinetics in mammalian species of veterinary interest – an overview

Doxycycline is a broad-spectrum tetracycline antibiotic widely used in veterinary medicine. The current review aims to summarise the available data about pharmacokinetics in mammalian species of veterinary interest and to indicate the basic strategies for refining dosage regimens in order to use this antibiotic reasonably. Additionally, the available data about population pharmacokinetics are reviewed as this approach exhibits a number of benefits in terms of determination of drug phar­ma­cokinetics, prediction of drug disposition and interpretation of the variations in the pharmacokinetic parameters. Further research with animal species of veterinary interest and pathogens causing diseases in animals is needed to clarify the pharmacokinetics and pharmacodynamics of doxycycline.

A molecularly imprinted antibiotic receptor on magnetic nanotubes for the detection and removal of environmental oxytetracycline.

The detection and elimination of antibiotic contaminants, such as oxytetracycline (OTC), a broad-spectrum tetracycline antibiotic, would be of help in efficient environmental monitoring, agriculture and food safety tests. Nevertheless, currently available methodologies, which mostly rely on the chromatographic separation of OTC, suffer from low sensitivity and complicated processes. Thus, we report here on the design and synthesis of a fluorescent sensor based on molecularly imprinted magnetic halloysite nanotubes (referred to as MHNTs@FMIPs) for the effective detection and purification of OTC in actual environmental samples. The fluorescence of the MHNTs@FMIPs was quenched obviously upon loading with OTC, covering a linear concentration range of 10-300 nM with a limit of detection (LOD) as low as 8.1 nM. The imprinting factor is 4.47, indicating an excellent specificity. Furthermore, the MHNTs@FMIPs can be applied to the quantitative detection of OTC (5 cycles of 300 nM) in aquaculture wastewater and Yangtze River water, demonstrating their immense application potential.

Activity of the Novel Aminomethylcycline KBP-7072 and Comparators against 1,057 Geographically Diverse Recent Clinical Isolates from the SENTRY Surveillance Program, 2019.

ABSTRACTKBP-7072 is a novel broad-spectrum tetracycline (aminomethylcycline) antibacterial in clinical development (oral and intravenous formulations) for the treatment of acute bacterial skin and skin structure infections, community-acquired bacterial pneumonia, and complicated intra-abdominal infections. KBP-7072 is active against many of the World Health Organization priority pathogens. In this study, KBP-7072 and tetracycline class comparators were susceptibility tested against 1,057 geographically diverse surveillance isolates from 2019 according to Clinical and Laboratory Standards Institute (CLSI) guidelines. KBP-7072 demonstrated potent in vitro activity against Gram-positive and Gram-negative bacterial pathogens. KBP-7072 was active against Staphylococcus aureus (MIC50/90, 0.06/0.12 mg/liter), methicillin-resistant S. aureus (MIC50/90, 0.06/0.12 mg/liter), S. lugdunensis (MIC50/90, 0.03/0.03 mg/liter), and other coagulase-negative staphylococci (MIC50/90, 0.06/0.25 mg/liter). KBP-7072 was active against Enterococcus faecalis (MIC50/90, 0.03/0.06 mg/liter) and vancomycin-susceptible and -nonsusceptible E. faecium (MIC50/90, 0.03/0.03 mg/liter); Streptococcus pneumoniae (MIC50/90, ≤0.015/0.03 mg/liter), including penicillin- and tetracycline-resistant strains; S. agalactiae (MIC50/90, 0.03/0.06 mg/liter), including macrolide-resistant strains; S. pyogenes (MIC50/90, 0.03/0.03 mg/liter); and viridans group streptococci, including S. anginosus group (MIC50/90, ≤0.015/0.03 mg/liter) isolates. KBP-7072 inhibited 90.2% (MIC50/90, 0.25/2 mg/liter) of all Enterobacterales isolates, including expanded-spectrum β-lactamase-phenotype strains at ≤2 mg/liter. KBP-7072 demonstrated potent activity against Acinetobacter baumannii-calcoaceticus species complex and Stenotrophomonas maltophilia isolates (MIC50/90 values, 0.5/1 mg/liter), Haemophilus influenzae (MIC50/90, 0.12/0.25 mg/liter; 100.0% inhibited at ≤0.25 mg/liter), and Moraxella catarrhalis (MIC50/90, 0.06/0.06 mg/liter). Based on MIC90 values, KBP-7072 in vitro activity was generally superior to that the other tetracycline class comparators tested. The potent activity of KBP-7072, including resistant organism groups, merits further clinical investigation in infections where these organisms are likely to occur.

Changes in Gut Microbiota Induced by Doxycycline Influence in Vascular Function and Development of Hypertension in DOCA-Salt Rats.

Previous experiments in animals and humans show that shifts in microbiota and its metabolites are linked to hypertension. The present study investigates whether doxycycline (DOX, a broad-spectrum tetracycline antibiotic) improves dysbiosis, prevent cardiovascular pathology and attenuate hypertension in deoxycorticosterone acetate (DOCA)-salt rats, a renin-independent model of hypertension. Male Wistar rats were randomly assigned to three groups: control, DOCA-salt hypertensive rats, DOCA-salt treated with DOX for 4 weeks. DOX decreased systolic blood pressure, improving endothelial dysfunction and reducing aortic oxidative stress and inflammation. DOX decreased lactate-producing bacterial population and plasma lactate levels, improved gut barrier integrity, normalized endotoxemia, plasma noradrenaline levels and restored the Treg content in aorta. These data demonstrate that DOX through direct effects on gut microbiota and its non-microbial effects (anti-inflammatory and immunomodulatory) reduces endothelial dysfunction and the increase in blood pressure in this low-renin form of hypertension.

Minocycline attenuates oxycodone-induced positive subjective responses in non-dependent, recreational opioid users

BackgroundRecent data suggest that glial cells may be involved in the analgesic effects and abuse liability of opioids. Preclinical studies have demonstrated that mu-opioid-receptor-selective agonists, such as oxycodone, activate glia and increase the release of cytokines, causing a suppression of opioid-induced analgesic effects. Preclinical studies also show that certain medications, such as the broad-spectrum tetracycline antibiotic minocycline, inhibit opioid-induced glial activation and thereby enhance the analgesic effects of opioids. Importantly, minocycline reduces the rewarding effects of opioids at the same doses that it enhances opioid-induced analgesia. AimsThe purpose of the present study was to assess the effects of acute administration of minocycline on the subjective, physiological, and analgesic effects of oxycodone in human research volunteers. DesignThis study was a within-subject, randomized, double-blind outpatient study. Participants completed five separate sessions in which they received 0, 100, or 200 mg minocycline (MINO) simultaneously with either 0 or 40 mg oxycodone (OXY). The subjective, physiological, and analgesic effects of OXY were measured before and repeatedly after drug administration. Settings and participantsParticipants were between 21 and 45 years of age, non-treatment seeking, non-dependent recreational opioid users (N = 12). This study was conducted between 2013 and 2014 at the New York State Psychiatric Institute in New York, NY. FindingsMINO 100 and 200 mg were safe and well-tolerated in combination with OXY 40 mg. MINO 200 mg administered with OXY 40 mg attenuated OXY-induced positive subjective effects such as “Good Effect” and “Liking” compared to OXY alone. MINO did not alter the physiological or analgesic effects of OXY. ConclusionsMINO may attenuate the abuse liability of mu-opioid-receptor-selective agonists.

Minocycline decreases CCR2-positive monocytes in the retina and ameliorates photoreceptor degeneration in a mouse model of retinitis pigmentosa.

Retinal inflammation accelerates photoreceptor cell death caused by retinal degeneration. Minocycline, a semisynthetic broad-spectrum tetracycline antibiotic, has been previously reported to rescue photoreceptor cell death in retinal degeneration. We examined the effect of minocycline on retinal photoreceptor degeneration using c-mer proto-oncogene tyrosine kinase (Mertk)-/-Cx3cr1GFP/+Ccr2RFP/+ mice, which enabled the observation of CX3CR1-green fluorescent protein (GFP)- and CCR2-red fluorescent protein (RFP)-positive macrophages by fluorescence. Retinas of Mertk-/-Cx3cr1GFP/+Ccr2RFP/+ mice showed photoreceptor degeneration and accumulation of GFP- and RFP-positive macrophages in the outer retina and subretinal space at 6 weeks of age. Mertk-/-Cx3cr1GFP/+Ccr2RFP/+ mice were intraperitoneally administered minocycline. The number of CCR2-RFP positive cells significantly decreased after minocycline treatment. Furthermore, minocycline administration resulted in partial reversal of the thinning of the outer nuclear layer and decreased the number of apoptotic cells, as assessed by the TUNEL assay, in Mertk-/-Cx3cr1GFP/+Ccr2RFP/+ mice. In conclusion, we found that minocycline ameliorated photoreceptor cell death in an inherited photoreceptor degeneration model due to Mertk gene deficiency and has an inhibitory effect on CCR2 positive macrophages, which is likely to be a neuroprotective mechanism of minocycline.

Impeding Minocycline Induced Hyperpigmentation by Pomegranate Extracting the Epidermis of Guinea Pig

Objective: This study was planned over the hypothesis that pomegranate extract rich in ellagic acid used with minocycline could decrease its adverse effect and prolong its therapeutic use and efficacy. Study design and Setting: This experimental study was done in the department of anatomy, Basic Medical Sciences Institute, Jinnah Postgraduate Medical Center, Karachi, Methodology: We acquired 40 guinea pigs (male, adult, 450 – 550 gm), randomly divided them into 4 groups.Group B received 0.0003mg/g bodyweight of minocycline only, group C was given 0.0003mg/g bodyweight of minocycline with 0.4mg/g bodyweight of pomegranate, group D was given 0.4mg/g bodyweight pomegranate only; with keeping group A with no intervention at laboratory diet for 8 weeks. After the experimental period, the animals were sacrificed, H & E and DOPA-OXIDASE staining was done on harvested skin tissues for morphometric observations under light microscopy. Results: The results showed that minocycline induced reduction in mean thickness of epidermis and increased melanin pigment deposition. Mean number of melanocytes decreased with pomegranate use though the difference was insignificant (P-value > 0.05) but consistent and measurable. Conclusions: It was proven that by including pomegranate in our daily diet, the process of hyperpigmentation of skin induced by the broad spectrum tetracycline particularly minocycline, can be slow down by decreasing the activity of tyrosinase enzyme, thus it provides a novel pathway to fight against any other drug induced hyperpigmentation occurring due to increase activity of tyrosinase enzyme

<p>Sarecycline: A Review of Preclinical and Clinical Evidence</p>

Sarecycline is a tetracycline-derived oral antibiotic, specifically designed for acne, and is approved by the Food and Drug Administration (FDA) in 2018 for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris (AV) in patients 9 years of age and older. It has been decades since a novel systemic antibiotic was approved to treat AV, a disease that affects up to 90% of teenagers and young adults worldwide and lasts well into adulthood. Sarecycline holds promise to yield fewer side effects than other commonly used broad-spectrum tetracyclines, including minocycline and doxycycline. The narrower spectrum of antibacterial activity of sarecycline, which specifically targets C. acnes and some Gram-positive bacteria with little or no activity against Gram-negative bacteria, suggests not only the potential for reduced emergence of antibiotic-resistant bacterial strains but also less disruption of the human gut microflora. Here, we review the key preclinical and clinical evidence on sarecycline.

Co3O4 nanoparticles/graphitic carbon nitride heterojunction for photoelectrochemical aptasensor of oxytetracycline

As a broad-spectrum tetracycline antibiotic, the overuse of oxytetracycline (OTC) causes antibiotics residues in the environment and seriously threats to human health owing to effective antibacterial properties. Thus, it is particularly important to design a photoelectrochemical (PEC) aptasensor to detect OTC with excellent performance. Herein, we developed a selective and stable PEC aptasensor of OTC on the basis of Co3O4 nanoparticles (Co3O4 NPs)/graphitic carbon nitride (g-CN) heterojunction, used as PEC active materials. The Co3O4 NPs were successfully grown on the g-CN via grinding and calcining mixture of Co3O4 precursors and bulk g-CN. The Co3O4/g-CN heterojunction with improved light utilization and promoted electrons/holes separation capability can exhibit higher PEC signal than that of g-CN. In order to implement the purpose of specific recognition, OTC-aptamer was introduced into modified electrode to construct highly selective PEC aptasensor for OTC determination, which can possess wide linear range (0.01–500 nM) with low detection limit (3.5 pM, S/N = 3). This PEC aptasensor platform with excellent selectivity and high stability can provide a practical application in the field of water monitoring.

Tetracycline-inactivating enzymes from environmental, human commensal, and pathogenic bacteria cause broad-spectrum tetracycline resistance

Tetracycline resistance by antibiotic inactivation was first identified in commensal organisms but has since been reported in environmental and pathogenic microbes. Here, we identify and characterize an expanded pool of tet(X)-like genes in environmental and human commensal metagenomes via inactivation by antibiotic selection of metagenomic libraries. These genes formed two distinct clades according to habitat of origin, and resistance phenotypes were similarly correlated. Each gene isolated from the human gut encodes resistance to all tetracyclines tested, including eravacycline and omadacycline. We report a biochemical and structural characterization of one enzyme, Tet(X7). Further, we identify Tet(X7) in a clinical Pseudomonas aeruginosa isolate and demonstrate its contribution to tetracycline resistance. Lastly, we show anhydrotetracycline and semi-synthetic analogues inhibit Tet(X7) to prevent enzymatic tetracycline degradation and increase tetracycline efficacy against strains expressing tet(X7). This work improves our understanding of resistance by tetracycline-inactivation and provides the foundation for an inhibition-based strategy for countering resistance.

Construction of nitrogen and phosphorus co-doped graphene quantum dots/Bi5O7I composites for accelerated charge separation and enhanced photocatalytic degradation performance

Nitrogen and phosphorus co-doped graphene quantum dot-modified Bi5O7I (NPG/Bi5O7I) nanorods were fabricated via a simple solvothermal method. The morphology, structure, and optical properties of the as-prepared samples were investigated by X-ray diffraction, scanning electron microscopy, high-resolution transmission electron microscopy, X-ray photoelectron spectroscopy (XPS), and diffused reflectance spectroscopy. The photocatalytic performance was estimated by degrading the broad-spectrum antibiotics tetracycline and enrofloxacin under visible light irradiation. The photodegradation activity of Bi5O7I improved after its surface was modified with NPGs, which was attributed to an increase in the photogenerated charge transport rate and a decrease in the electron-hole pair recombination efficiency. From the electron spin resonance spectra, XPS valence band data, and free radical trapping experiment results, the main active substances involved in the photocatalytic degradation process were determined to be photogenerated holes and superoxide radicals. A possible photocatalytic degradation mechanism for NPG/Bi5O7I nanorods was proposed.

Synthesis, Characterization and In Vitro Antibacterial Derivatives of Doxycycline

Objective: Nowadays antibacterial drugs resistance is major problem in the world. To overcome this problem, some novel derivates of doxycycline were synthesized by single step condensation reaction with ten different types of aromatic and aliphatic aldehydes and ketones in ethanol as solvent and acetic acid as catalyst. In these reactions, deprotonation of primary amine occurs that results in formation of imine. 
 Methods: All the derivatives physically characterized and confirmed by analytical techniques i.e. FTIR and 1H NMR and 13C NMR. The derived compounds have exhibited significantly more active against both gram positive as well as gram negative bacterial strains as compared to parent drug.
 Results: Derived Schiff bases RDC2, RDC4 and RDC10 showed zone of inhibition against Bacillus subtilis as compared to doxycycline and derived Schiff bases RDC1, RDC2, RDC5, RDC6, RDC7 and RDC8 showed more zone of inhibition against Micrococcus luteus as compared to doxycycline. Yield (75%), m.p. 180-185°C, Mol. Wt. 1063, Elemental Analysis: (Calculated) for C58H54N4O16: iC, 65.53; H, 5.12; N, 5.27; (Found): C, 65.49; H, 5.18; N, 5.37; FTIR (ν, cm‐1): 3066 (=C-H), 1665(C=N), 1585, 1490(C=C, phenyl), 3650(OH), 1692 (C=O); 1H NMR (DMSO−d6, δ, ppm), 6.02-6.03 d, 6.91-6.92 d, (=CH-); 6.88-6.89 t (=CH), 2.89-2.90 d, (-CH); 1.07-1.08 q, (-CH3), 3.38-3.39 d; 3.17-3.18 d, (CH), 1.47-1.48 t (CH), 1.48 s, (CH3), 6.96-6.97d, 7.577-7.588 d, (-CH=) 15.21 s (OH); 4.62 s (OH); 1.46-1.47 s (OH); 13C NMR (DMSO−d6, δ, ppm).
 Conclusion: Doxycycline is among broad-spectrum tetracycline. The Schiff bases derived from doxycycline show significantly highly active against gram negative bacteria as compared to doxycycline. In future further study on these derived compounds will help in market new derivative of doxycycline, which will have more broad-spectrum activity than doxycycline.

Effect of doxycyline in chronic obstructive pulmonary disease - An exploratory study

PurposeVarious mechanisms, including oxidative stress, inflammation, and protease-antiprotease imbalance are proposed for the progressive decline in lung function in chronic obstructive pulmonary disease (COPD). Doxycycline, a broad spectrum tetracycline antibiotic, is reported to have non-antimicrobial matrix metalloproteinases (MMP) inhibitory action in various inflammatory conditions. The effect of doxycycline in COPD is hereby assessed in the present randomized prospective study. Patients and methodsThe first group of COPD patients (n = 30; mild (n = 3), moderate (n = 6), severe (n = 7), very severe (n = 14) as per GOLD II & III criteria was prescribed the standard therapy, a combination of (i) short acting anti-muscarinic agent (SAMA) + short acting β2 agonist (SABA) inhaled and (ii) corticosteroid inhaled (ICS) + long acting β2 agonist (LABA) (iii) ICS + LABA + LAMA. Whereas doxycycline (100 mg), was used daily once or twice as per Body Mass Index (BMI), as an add-on to existing standard therapy for the second group of patients (n = 30; mild (n = 2), moderate (n = 7), severe (n = 8), very severe (n = 13). All recruited patients were followed-up after 3 months of treatment. Lung function index FEV1(%) predicted, FEV1/FVC (%), quality of life status including COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ) were assessed. Routine blood cell count also was performed. ResultsBiochemical analysis included estimation of oxidative stress markers, inflammatory cytokines and proteases in plasma of both the groups. Reduction in oxidative stress is evidenced by a significant decrease in Lipid hydro peroxides (LPO), total oxidative stress (TOS) and increase in glutathione peroxidase (GSH-PX), reduced glutathione (GSH) and total anti-oxidant capacity (TAO) nitrite and nitrate (NOx) along with peroxynitrate following 3 months of add-on doxycycline treatment. Reduced levels of cytokines such as interleukin IL-6, TNF-α, IL-8 were also observed. Multivariate analysis identified TNF-α major effective discriminant among pre and post doxycycline treated COPD patients. The expression of TNF-α was inversely correlated with FEV1/FVC (%) changes. The levels of MMP-2 and MMP-9/tissue inhibitors of metalloproteinases (TIMP)-1 ratio (MMP-9/ TIMP-1), also decreased significantly and the decline could be associated with TOS. A significant increase in bilirubin and reduced glutathione (GSH) level was noticed in standard therapy group. ConclusionThese data suggest that the improvement in lung function and quality of life in COPD patients may probably be attributed to the antioxidant, anti-inflammatory and anti-MMP activity of doxycycline. The potential therapeutic role of long-term doxycycline, in addition to its traditional antibiotic effect, definitely warrants further attention.

Sarecycline hydrochloride for the treatment of acne vulgaris.

Sarecycline hydrochloride (Seysara) is a novel, narrow-spectrum tetracycline derivative approved by the U.S. Food and Drug Administration (FDA) in October 2018 for the treatment of inflammatory non-nodular moderate to severe acne vulgaris. It was initially developed by Paratek Pharmaceuticals, Inc. (U.S.) and Allergan plc (U.S.), which later was acquired by Almirall S.A. (Barcelona, Spain). Almirall S.A. obtained U.S. FDA approval of oral sarecycline tablets under the trade name Seysara. Sarecycline exhibits antibacterial activity against important skin/soft tissue pathogens with targeted activity against Cutibacterium acnes--an anaerobic Gram-positive bacterium linked with acne lesions--and also exerts anti-inflammatory effects as do other tetracyclines used in the treatment of acne vulgaris. Interestingly, unlike the broad-spectrum tetracyclines, sarecycline is less potent against aerobic Gram-negative bacilli and anaerobic bacteria associated with endogenous intestinal microbial flora. This provides it with a more specific antibacterial spectra with lower chances of adverse off-target antibacterial effects, thus making it a promising choice of treatment over others in its class. It has also demonstrated low propensity to resistance as compared with other tetracyclines and is also active against tetracycline-resistant Staphylococcus aureus as well as erythromycin- and clindamycin-resistant C. acnes strains. Sarecycline has successfully undergone numerous phase I, phase II and three phase III studies establishing it as a well-tolerated once-daily oral drug available as a tablet for the treatment of patients 9 years of age or above.

Minocycline susceptibility breakpoints for Acinetobacter baumannii: do we need to re-evaluate them?

Minocycline is an old broad-spectrum tetracycline indicated for the treatment of various infections, including those due to minocycline-susceptible Acinetobacter spp. Susceptibility data worldwide are showing increasing rates of resistance of Acinetobacter baumannii to almost all antimicrobial classes, whereas minocycline seems to remain relatively potent against this significant pathogen. Since no new effective drugs have been released against MDR A. baumannii, minocycline is an attractive choice. Tracing back minocycline CLSI susceptibility breakpoints, it is evident that they have been based on old pharmacokinetic approaches. In an attempt to integrate the scarce new pharmacodynamic data, a Monte Carlo simulation was performed. It seems that the currently used breakpoints are, 8-fold elevated according to the approved dosage regimen, giving erroneously higher rates of minocycline susceptibility of A. baumannii. Therefore, current minocycline breakpoints merit re-evaluation in order to deliver reliable susceptibility profiles for selecting the appropriate therapy.

Drug-Induced Autoimmune Hepatitis in a Patient Treated With Minocycline: A Rare Adverse Effect

Minocycline is an oral broad-spectrum tetracycline antibiotic that is used to treat moderate to severe acne vulgaris as well as certain sexually transmitted infections. Minocycline-induced autoimmune hepatitis can be differentiated from “classic” autoimmune hepatitis by the patient's swift recovery after discontinuing the offending drug and no relapse of the condition upon discontinuation of treatment with corticosteroids. A 31-year-old Chinese woman, with past medical history of acne vulgaris, presented to the Emergency Department with nausea, vomiting, and abdominal pain for the last 3-4 days. She had experienced three episodes of non-bloody, non-bilious vomiting. She described a persistent dull aching pain in the right upper quadrant of the abdomen that had been increasing in intensity, particularly over the last two days. She denied any recent change in her diet. She reported that no one in her household had experienced similar symptoms. She denied any additional recent symptoms. Upon medication reconciliation, it was discovered that the patient had been taking minocycline, on her own and not under medical supervision, for the past three months. Initial laboratory testing was remarkable for significantly elevated transaminase levels with aspartate aminotransferase (AST) of 718 U/L (10-35 U/L) and alanine aminotransferase (ALT) of 1138 U/L (10-55 U/L). An autoimmune workup revealed an elevated antinuclear antibody (ANA) titer (1:160) (<1:40), positive anti-smooth muscle antibodies (ASMA), and the finding of hypergammaglobulinemia (3.2 g/dL) (0.7-1.6 g/dL) with elevated levels of serum immunoglobulin G (IgG) (3176 mg/dL) (700-1600 mg/dL). The bilirubin levels decreased steadily from Day 1 of the hospital admission, but the transaminase levels continued to rise despite discontinuation of the minocycline (Figure 2). On Day 7, she was started on treatment with prednisolone. Also, an IR-guided liver biopsy was performed for the purpose of confirming the diagnosis as well as to assess the degree of liver injury (Figure 3). After two days of treatment with prednisolone, the patient's transaminase levels began to decrease steadily (Figure 2). Physicians should be informed about and suspect drug-induced hepatitis for any individual taking minocycline who presents with elevated LFTs. Physicians who prescribe it to treat acne vulgaris should be aware of this potentially severe adverse effect and stop it immediately when suspicion is raised.2316_B Figure 2. Changes in total bilirubin and alanine aminotransferase (ALT) before and after treatment with prednisolone *Prednisolone, at an initial dose of 50 mg/day, was started on Day 7 of the hospital admission.2316_C Figure 3. Figure 3 (A, B, C, D; left to right). Histopathologic images of the patient's drug-induced hepatitis from liver biopsy A) Piecemeal necrosis. There is chronic inflammation in the portal tracts. H&E stain. 100x. B) Again, there is chronic inflammation in the portal tracts with many plasma cells, lymphocytes, and occasional eosinophils. H&E stain. 400x. C) and D) Spotty necrosis. There is mild chronic inflammation in the portal tracts, as well as ballooning degeneration of hepatocytes indicative of hepatocellular injury. H&E stain. 100x and 400x, respectively.2316_A Figure 1. Abdominal ultrasound There is mild hepatomegaly with increased liver echogenicity.

Thermodynamic studies of iron chelation with doxycycline in acidic medium

Doxycycline (DOX) is a broad-spectrum tetracycline antibiotic synthetically derived from oxytetracycline. The complex formation of this drug with iron(III) was studied using spectrophotometry. The thermodynamic parameters of the systems were calculated using the changes in the absorption spectra which occur due to hydrogen bond or complex formation. Thermodynamic parameters of the formation of iron(III) complex with doxycycline (ΔH, ΔG, ΔS, and stability constants) were determined spectrophotometrically at a wavelength corresponding to absorption maximum (374.5 nm) at three different temperatures (22, 35, and 45°C). The obtained data show that the complex has metal to ligand molar ratio of 1: 2 at pH 2–3. The stability constants were calculated to be 13.99 × 106, 7.06 × 105, and 1.29 × 106 by mole ratio method at 22, 35, and 45°C, respectively.

Antibiotic-non-antibiotic combinations for combating extremely drug-resistant Gram-negative 'superbugs'.

The emergence of antimicrobial resistance of Gram-negative pathogens has become a worldwide crisis. The status quo for combating resistance is to employ synergistic combinations of antibiotics. Faced with this fast-approaching post-antibiotic era, it is critical that we devise strategies to prolong and maximize the clinical efficacy of existing antibiotics. Unfortunately, reports of extremely drug-resistant (XDR) Gram-negative pathogens have become more common. Combining antibiotics such as polymyxin B or the broad-spectrum tetracycline and minocycline with various FDA-approved non-antibiotic drugs have emerged as a novel combination strategy against otherwise untreatable XDR pathogens. This review surveys the available literature on the potential benefits of employing antibiotic-non-antibiotic drug combination therapy. The apex of this review highlights the clinical utility of this novel therapeutic strategy for combating infections caused by 'superbugs'.

Process Development and Scale-up of Fully Synthetic Tetracycline TP-2758: A Potent Antibacterial Agent with Excellent Oral Bioavailability

Process research and development of the fully synthetic broad spectrum tetracycline TP-2758, with a chiral pyrrolidine side chain at the C-8 position, is described. The process utilizes two key intermediates, 7 and 10, in a convergent approach that allows for manufacturing of sufficient quantities of API to supply preclinical and early clinical development. The pyrrolidine moiety was introduced into the left-hand piece (LHP) 10 with high enantioselectivity using Ellman’s sulfinamide chemistry, and the absolute configuration was confirmed by X-ray crystal structure analysis.

Minocycline does not evoke anxiolytic and antidepressant-like effects in C57BL/6 mice

Minocycline is a broad-spectrum tetracycline antibiotic with multiple actions, including anti-inflammatory and neuroprotective effects, that was proposed as novel treatment for several psychiatric disorders including schizophrenia and depression. However, there are contradictory results regarding antidepressant effects of minocycline in rodent models. Additionally, the possible anxiolytic effect of minocycline is still poorly investigated. Therefore, we aimed to clarify in the present study the influence of minocycline on behavioral correlates of mood disorders in standard tests for depression and anxiety, the Porsolt Forced Swim Test (FST), Elevated O-Maze, Dark–Light Box Test and Openfield Test in adult C57BL/6 mice. We found, unexpectedly, that mice treated with minocycline (20–40mg/kg, i.p.) did not display antidepressant- or anxiolytic-like behavioral changes in contrast to mice treated with diazepam (0.5mg/kg, anxiety tests) or imipramine (20mg/kg, depressive-like behavior). These results are relevant for future studies, considering that C57BL/6 mice, the most widely used strain in pharmacological and genetic animal models, did not react as expected to the treatment regime applied.