Group items tagged

Studies of similar meshes that are used in hernia repair have demonstrated that all polypropylene meshes induce a prolonged inflammatory response at the site of implantation

the long-term presence of activated inflammatory cells, such as macrophages at the mesh tissue interface, can impact negatively the ability of the mesh to function as intended.

All M1 proinflammatory and M2 proremodeling cytokines and chemokines were increased in mesh explants as compared with nonmesh tissue (Table 3Table 3), which indicated a robust, active, and ongoing host response to polypropylene long after implantation

Comparison of the ratio of the M2 proremodeling cytokines (IL-10+IL-4) with the M1 proinflammatory cytokines (TNF-α+IL-12p70) revealed a decrease in mesh explants as compared with controls (P = .003), which indicated a shift towards a proinflammatory profile.

Mesh explants contained a higher number of total cells/×200 field when compared with controls (682.46 ± 142.61 cells vs 441.63 ± 126.13 cells; P < .001) and a lower ratio of M2:M1 macrophages (0.260 ± 0.161 cells vs 1.772 ± 1.919; P = .001), which supported an ongoing proinflammatory response.

the host response was proportional to the amount of material in contact with the host

A persistent foreign body response was observed in mesh-tissue complexes that were excised from women who required surgical excision of mesh months to years after mesh implantation

The host response was characterized by a predominance of macrophages with an increase in both proinflammatory and proremodeling cytokines/chemokines along with increased tissue degradation, as evidenced by increased MMP-2 and -9

Mesh-tissue complexes removed for mesh exposure had increased pro–MMP-9 that indicated a proinflammatory and tissue destruction–type response

The presence of macrophages, elevated cytokines, chemokines, and MMPs in tissue-mesh complexes that were excised from patients with exposure or pain suggests that polypropylene mesh elicits an ongoing host inflammatory response

In the presence of a permanent foreign body, the implant is surrounded with a fibrotic capsule because it cannot be degraded

For hernia meshes, if the fibers are too close (<1 mm), the fibrotic response to neighboring fibers overlaps, or “bridges,” and results in “bridging fibrosis” or encapsulation of the mesh

Gynemesh PS has a highly unstable geometry when loaded that resulted in pore collapse and increasing stiffness of the product

mesh shrinkage (50-70%) has been described to occur after transvaginal insertion of prolapse meshes

Under steady-state conditions, intracellular GSH is maintained at millimolar concentrations, which keeps cells in a reduced environment and serves as the principal intracellular redox buffer when cells are subjected to an oxidative stressor including H2O2 (26). Glutathione peroxidase (GPx) activity catalyzes the reduction of H2O2 to water with the conversion of GSH to glutathione disulfide (GSSG). Under steady-state conditions, GSSG is recycled back to GSH by glutathione disulfide reductase using reducing equivalents from NADPH. However, under conditions of increased H2O2 flux, this recycling mechanism may become overwhelmed leading to a depletion of intracellular GSH (27, 28).

ascorbate radiosensitization can create an overwhelming oxidative stress to pancreatic cancer cells resulting in oxidation/depletion of the GSH intracellular redox buffer, resulting in cell death.

Treatment with the combination of ascorbate + IR significantly delayed tumor growth compared to controls or ascorbate alone

Ascorbate + IR also significantly increased overall survival compared to controls, IR alone or ascorbate alone

54% of mice treated with the combination of IR + ascorbate had no measurable tumors

Glutathione is a measurable marker indicative of the oxidation state of the thiol redox buffer in cells. In severe systemic oxidative stress, the GSSG/2GSH couple may become oxidized, i.e. the concentration of GSH decreases and GSSG may increase because the capacity to recycle GSSG to GSH becomes rate-limiting

This suggests that the very high levels of pharmacological ascorbate in these experiments may have a pro-oxidant toward red blood cells as seen by a decrease in the capacity of the intracellular redox buffer

These data support the hypothesis that ascorbate radiosensitization does not cause an increase in oxidative damage from lipid-derived aldehydes to other organs.

Our current study demonstrates the potential for pharmacological ascorbate as a radiosensitizer in the treatment of pancreatic cancer.

pharmacological ascorbate enhances IR-induced cell killing and DNA fragmentation leading to induction of apoptosis in HL60 leukemia cells

pharmacological ascorbate significantly decreases clonogenic survival and inhibits the growth of all pancreatic cancer cell lines as a single agent, as well as sensitizes cancer cells to IR

Hurst et al. demonstrated that pharmacological ascorbate combined with IR leads to increased numbers of double-strand DNA breaks and cell cycle arrest when compared to either treatment alone

pharmacological ascorbate could serve as a “pro-drug” for the delivery of H2O2 to tumors

the double-strand breaks induced by H2O2 were more slowly repaired

The combination of ascorbate and IR provide two distinct mechanisms of action: ascorbate-induced toxicity due to extracellular production of H2O2 that then diffuses into cells and causes damage to DNA, protein, and lipids; and radiation-induced toxicity as a result of ROS-induced damage to DNA. In addition, redox metal metals like Fe2+ may play an important role in ascorbate-induced cytotoxicity. By catalyzing the oxidation of ascorbate, labile iron can enhance the rate of formation of H2O2; labile iron can also react with H2O2. Recently our group has demonstrated that pharmacological ascorbate and IR increase the labile iron in tumor homogenates from this murine model of pancreatic cancer

we demonstrated that ascorbate or IR alone decreased tumor growth, but the combination treatment further inhibited tumor growth, indicating that pharmacological ascorbate is an effective radiosensitizer in vivo

data suggest that pharmacological ascorbate may protect the gut locally by decreasing IR-induced damage to the crypt cells, and systemically, by ameliorating increases in TNF-α

A treatment dose of 4 g ascorbate/kg body weight either once or twice daily did not produce any discernible adverse effects

Xenograft experiments showed that parenteral ascorbate as the only treatment significantly decreased both tumor growth and weight by 41–53%

Peak plasma concentrations of ascorbate approached 30 mM

Pharmacologic concentrations of ascorbate decreased tumor volumes 41–53% in diverse cancer types known for both their aggressive growth and limited treatment options.

Our findings showed that pharmacologic ascorbic acid concentrations were cytotoxic to many types of cancer cells in vitro (Fig. 1A) and significantly impeded tumor progression in vivo without toxicity to normal tissues

The amelioration of ascorbate cytotoxicity in vitro by the addition of catalase was consistent among sensitive cancer cells (Fig. 1B) and points unambiguously to H2O2 generation in the extracellular medium

the current in vivo data support that pharmacologic ascorbate concentrations, which can readily be achieved in humans (Fig. 3E), diminished growth of several aggressive cancer types in mice (Fig. 2) without causing apparent adverse effects.

These intratumoral H2O2 concentrations of >125 μM persisted for >3 h after ascorbate administration

Data from the American Cancer Society show that the rate of increase in cancer deaths/year (3.4%) was two-fold greater than the rate of increase in new cases/year (1.7%) from 2013 to 2017

cancer is predicted to overtake heart disease as the leading cause of death in Western societies

cancer can also be recognized as a metabolic disease.

glucose is first split into two molecules of pyruvate through the Embden–Meyerhof–Parnas glycolytic pathway in the cytosol

Aerobic fermentation, on the other hand, involves the production of lactic acid under normoxic conditions

persistent lactic acid production in the presence of adequate oxygen is indicative of abnormal respiration

Otto Warburg first proposed that all cancers arise from damage to cellular respiration

The Crabtree effect is an artifact of the in vitro environment and involves the glucose-induced suppression of respiration with a corresponding elevation of lactic acid production even under hyperoxic (pO2 = 120–160 mmHg) conditions associated with cell culture

the Warburg theory of insufficient aerobic respiration remains as the most credible explanation for the origin of tumor cells [2, 37, 51, 52, 53, 54, 55, 56, 57].

The main points of Warburg’s theory are; 1) insufficient respiration is the predisposing initiator of tumorigenesis and ultimately cancer, 2) energy through glycolysis gradually compensates for insufficient energy through respiration, 3) cancer cells continue to produce lactic acid in the presence of oxygen, and 4) respiratory insufficiency eventually becomes irreversible

Efraim Racker coined the term “Warburg effect”, which refers to the aerobic glycolysis that occurs in cancer cells

Warburg clearly demonstrated that aerobic fermentation (aerobic glycolysis) is an effect, and not the cause, of insufficient respiration

all tumor cells that have been examined to date contain abnormalities in the content or composition of cardiolipin

The evidence supporting Warburg’s original theory comes from a broad range of cancers and is now overwhelming

respiratory insufficiency, arising from any number mitochondrial defects, can contribute to the fermentation metabolism seen in tumor cells.

data from the nuclear and mitochondrial transfer experiments suggest that oncogene changes are effects, rather than causes, of tumorigenesis

Normal mitochondria can suppress tumorigenesis, whereas abnormal mitochondria can enhance tumorigenesis

In addition to glucose, cancer cells also rely heavily on glutamine for growth and survival

Glutamine is anapleurotic and can be rapidly metabolized to glutamate and then to α-ketoglutarate for entry into the TCA cycle

Glucose and glutamine act synergistically for driving rapid tumor cell growth

Glutamine metabolism can produce ATP from the TCA cycle under aerobic conditions

Amino acid fermentation can generate energy through TCA cycle substrate level phosphorylation under hypoxic conditions

Hif-1α stabilization enhances aerobic fermentation

targeting glucose and glutamine will deprive the microenvironment of fermentable fuels

Although Warburg’s hypothesis on the origin of cancer has created confusion and controversy [37, 38, 39, 40], his hypothesis has never been disproved

Warburg referred to the phenomenon of enhanced glycolysis in cancer cells as “aerobic fermentation” to highlight the abnormal production of lactic acid in the presence of oxygen

Emerging evidence indicates that macrophages, or their fusion hybridization with neoplastic stem cells, are the origin of metastatic cancer cells

Radiation therapy can enhance fusion hybridization that could increase risk for invasive and metastatic tumor cells

Kamphorst et al. in showing that pancreatic ductal adenocarcinoma cells could obtain glutamine under nutrient poor conditions through lysosomal digestion of extracellular proteins

It will therefore become necessary to also target lysosomal digestion, under reduced glucose and glutamine conditions, to effectively manage those invasive and metastatic cancers that express cannibalism and phagocytosis.

Previous studies in yeast and mammalian cells show that disruption of aerobic respiration can cause mutations (loss of heterozygosity, chromosome instability, and epigenetic modifications etc.) in the nuclear genome

The somatic mutations and genomic instability seen in tumor cells thus arise from a protracted reliance on fermentation energy metabolism and a disruption of redox balance through excess oxidative stress.

According to the mitochondrial metabolic theory of cancer, the large genomic heterogeneity seen in tumor cells arises as a consequence, rather than as a cause, of mitochondrial dysfunction

A therapeutic strategy targeting the metabolic abnormality common to most tumor cells should therefore be more effective in managing cancer than would a strategy targeting genetic mutations that vary widely between tumors of the same histological grade and even within the same tumor

Tumor cells are more fit than normal cells to survive in the hypoxic niche of the tumor microenvironment

Hypoxic adaptation of tumor cells allows for them to avoid apoptosis due to their metabolic reprograming following a gradual loss of respiratory function

The high rates of tumor cell glycolysis and glutaminolysis will also make them resistant to apoptosis, ROS, and chemotherapy drugs

Despite having high levels of ROS, glutamate-derived from glutamine contributes to glutathione production that can protect tumor cells from ROS

It is clear that adaptability to environmental stress is greater in normal cells than in tumor cells, as normal cells can transition from the metabolism of glucose to the metabolism of ketone bodies when glucose becomes limiting

Mitochondrial respiratory chain defects will prevent tumor cells from using ketone bodies for energy

glycolysis-dependent tumor cells are less adaptable to metabolic stress than are the normal cells. This vulnerability can be exploited for targeting tumor cell energy metabolism

In contrast to dietary energy reduction, radiation and toxic drugs can damage the microenvironment and transform normal cells into tumor cells while also creating tumor cells that become highly resistant to drugs and radiation

Drug-resistant tumor cells arise in large part from the damage to respiration in bystander pre-cancerous cells

Because energy generated through substrate level phosphorylation is greater in tumor cells than in normal cells, tumor cells are more dependent than normal cells on the availability of fermentable fuels (glucose and glutamine)

Ketone bodies and fats are non-fermentable fuels

Although some tumor cells might appear to oxidize ketone bodies by the presence of ketolytic enzymes [181], it is not clear if ketone bodies and fats can provide sufficient energy for cell viability in the absence of glucose and glutamine

Apoptosis under energy stress is greater in tumor cells than in normal cells

A calorie restricted ketogenic diet or dietary energy reduction creates chronic metabolic stress in the body

. This energy stress acts as a press disturbance

Drugs that target availability of glucose and glutamine would act as pulse disturbances

Hyperbaric oxygen therapy can also be considered another pulse disturbance

The KD can more effectively reduce glucose and elevate blood ketone bodies than can CR alone making the KD potentially more therapeutic against tumors than CR

Campbell showed that tumor growth in rats is greater under high protein (>20%) than under low protein content (<10%) in the diet

Protein amino acids can be metabolized to glucose through the Cori cycle

The fats in KDs used clinically also contain more medium chain triglycerides

Calorie restriction, fasting, and restricted KDs are anti-angiogenic, anti-inflammatory, and pro-apoptotic and thus can target and eliminate tumor cells through multiple mechanisms

Ketogenic diets can also spare muscle protein, enhance immunity, and delay cancer cachexia, which is a major problem in managing metastatic cancer

GKI values of 1.0 or below are considered therapeutic

The GKI can therefore serve as a biomarker to assess the therapeutic efficacy of various diets in a broad range of cancers.

It is important to remember that insulin drives glycolysis through stimulation of the pyruvate dehydrogenase complex

The water-soluble ketone bodies (D-β-hydroxybutyrate and acetoacetate) are produced largely in the liver from adipocyte-derived fatty acids and ketogenic dietary fat. Ketone bodies bypass glycolysis and directly enter the mitochondria for metabolism to acetyl-CoA

Due to mitochondrial defects, tumor cells cannot exploit the therapeutic benefits of burning ketone bodies as normal cells would

Therapeutic ketosis with racemic ketone esters can also make it feasible to safely sustain hypoglycemia for inducing metabolic stress on cancer cells

ketone bodies can inhibit histone deacetylases (HDAC) [229]. HDAC inhibitors play a role in targeting the cancer epigenome

Therapeutic ketosis reduces circulating inflammatory markers, and ketones directly inhibit the NLRP3 inflammasome, an important pro-inflammatory pathway linked to carcinogenesis and an important target for cancer treatment response

Chronic psychological stress is known to promote tumorigenesis through elevations of blood glucose, glucocorticoids, catecholamines, and insulin-like growth factor (IGF-1)

In addition to calorie-restricted ketogenic diets, psychological stress management involving exercise, yoga, music etc. also act as press disturbances that can help reduce fatigue, depression, and anxiety in cancer patients and in animal models

Ketone supplementation has also been shown to reduce anxiety behavior in animal models

This physiological state also enhances the efficacy of chemotherapy and radiation therapy, while reducing the side effects

lower dosages of chemotherapeutic drugs can be used when administered together with calorie restriction or restricted ketogenic diets (KD-R)

Besides 2-DG, a range of other glycolysis inhibitors might also produce similar therapeutic effects when combined with the KD-R including 3-bromopyruvate, oxaloacetate, and lonidamine

A synergistic interaction of the KD diet plus radiation was seen

It is important to recognize, however, that the radiotherapy used in glioma patients can damage the respiration of normal cells and increase availability of glutamine in the microenvironment, which can increase risk of tumor recurrence especially when used together with the steroid drug dexamethasone

Poff and colleagues demonstrated that hyperbaric oxygen therapy (HBOT) enhanced the ability of the KD to reduce tumor growth and metastasis

HBOT also increases oxidative stress and membrane lipid peroxidation of GBM cells in vitro

The effects of the KD and HBOT can be enhanced with administration of exogenous ketones, which further suppressed tumor growth and metastasis

Besides HBOT, intravenous vitamin C and dichloroacetate (DCA) can also be used with the KD to selectively increase oxidative stress in tumor cells

Recent evidence also shows that ketone supplementation may enhance or preserve overall physical and mental health

Some tumors use glucose as a prime fuel for growth, whereas other tumors use glutamine as a prime fuel [102, 186, 262, 263, 264]. Glutamine-dependent tumors are generally less detectable than glucose-dependent under FDG-PET imaging, but could be detected under glutamine-based PET imaging

GBM and use glutamine as a major fuel

Many of the current treatments used for cancer management are based on the view that cancer is a genetic disease

Emerging evidence indicates that cancer is a mitochondrial metabolic disease that depends on availability of fermentable fuels for tumor cell growth and survival

Glucose and glutamine are the most abundant fermentable fuels present in the circulation and in the tumor microenvironment

Low-carbohydrate, high fat-ketogenic diets coupled with glycolysis inhibitors will reduce metabolic flux through the glycolytic and pentose phosphate pathways needed for synthesis of ATP, lipids, glutathione, and nucleotides

the overall response of MPS is not maximized. Instead, the limited availability of EAA likely explains the qualitative difference in magnitude of the MPS response to ingestion of BCAAs alone and ingestion of similar amounts of BCAAs as part of intact whey protein

decreased EAA concentrations following leucine ingestion

these data support the notion that EAA availability is the rate-limiting factor for stimulating a maximal MPS response to resistance exercise with BCAA ingestion

High density level of PGR in the TE was an independent prognostic factor for CF.

Our large-sized study demonstrates a wide distribution of PGR in stromal and epithelial cells of both benign and malignant prostate tissue

there seems to be a general agreement of PGR presence in the stromal cells of PCa

In line with our findings, several have also reported a high PGR expression in TE of PCa [9,10,23,25]. In contrast, others have demonstrated a total lack of PGR expression in TE

the actions of progesterone are tissue specific

In our work univariate analysis demonstrated a high PGR expression in TS to be associated with clinical failure in PCa patients. So far we have not yet demonstrated the mechanism underlying this association

Several non-genomic proliferative actions of progesterone have been proposed in tumor cells of other organs, including breast [35–37], astrocytoma [38] and osteosarcoma [39] cell lines. However, such results are contradicted by suggestions of anti-proliferative actions of progesterone in endometrial cancer

Yu et al. found PGR to be negatively regulating stromal cell proliferation in vitro

high PGR density level in TE was associated with CF in patients with Gleason score ≥ 7

Bonkhoff et al. have suggested progressive emergence of PGR during PCa progression and metastasis

Latil and co-workers found a decreased PGR expression in clinically localized tumors and increased PGR expression in hormone-refractory tumors, when compared with normal prostate tissue

Our findings provide further support to these findings, indicating that PGR plays a role in the pathogenesis of PCa

Ki67 and PGR in TE were correlated with CF (S3 Text), indicating an association between PGR and proliferative activity

The mechanism behind the PGR up-regulation in PCa has not yet been elucidated

The PGR is, like the glucocorticoid receptor, similar to androgen receptor with 88% sequence homology in the ligand-binding domain

progesterone induced expression of androgen receptor-regulated genes could be a potential mechanism contributing to the development of castrate resistant PCa

A possibility of different roles by the two PGR isoforms in normal prostate tissue and PCa, as is suggested for the estrogen receptors [13], must also be taken into account

principal action of histamine is to protect cytotoxic lymphocytes from myeloid-cell-induced inactivation, thus improving the efficiency of the T and NK cell stimulation achieved by IL-2

random-ized Phase II study of patients with renal cell carcinoma further support the suggestion that the combination of HDC and IL-2 improves lymphocyte functions

HDC improves the effectiveness of IL-2-induced T and NK cell activation in cancer patients, as predicted in preclinical models

The serum level of LDH correlated with tumor burden and was thought to reflect the tumor’s growth and invasive potential

the majority of patients with advanced or metastatic disease could be detected to have extremely high serum level of LDH

strong evidence to support effective chemotherapy of full dose even in patients with high LDH level

LDH is a key enzyme in the process of energy production in cancer cells, it catalyzes the conversion of pyruvate to lactate in hypoxic conditions

its function in anaerobic metabolism, cancer cells grow even after their rapid proliferation that leads to low-oxygen conditions in the tumor microenvironment

LDH plays an important role in tumor progression and maintenance

inhibition of LDH inhibits tumor progression and has been considered for the therapeutic target of cancer energy metabolism

LDH levels are increased in response to tissue injury or during disease states

LDH could be a marker of tumor burden for advanced cancer patients

Patients with higher inflammation or tumor burdens, as measured by CRP levels or tumor antigen levels, tend to show lower peak plasma ascorbate levels after IVC.

Patients with metastatic tumors tend to achieve lower post infusion plasma ascorbate levels than those with localized tumors.

The inflammatory microenvironment of cancer cells leads to increasing oxidative stress, which apparently depletes vitamin C, resulting in lower plasma ascorbate concentrations in blood samples post IVC infusion. Another explanation for this finding may be that cancers are themselves more metabolically active in their uptake of vitamin C, causing subjects to absorb more of the vitamin, and as a results show lower plasma ascorbate concentrations in blood post IVC infusion.

Most of the prostate cancer patients studied, 75±19% (95% confidence), showed reductions in PSA levels during the course of their IVC therapy

Laboratory studies suggest that, at high concentrations, ascorbate does not interfere with chemotherapy or irradiation and may enhance efficacy in some situations

Cameron and Pauling observed fourfold survival times in terminal cancer patients treated with intravenous ascorbate infusions followed by oral supplementation

Meta-analyses of clinical studies involving cancer and vitamins also conclude that antioxidant supplementation does not interfere with the efficacy of chemotherapeutic regiments

patients with severely elevated CRP levels attain plasma ascorbate concentrations after IVC infusions that are only 65% of those attained for subjects with normal CRP levels

The finding of decreased plasma ascorbate levels in cancer patients may relate to the molecular structure of ascorbic acid; in particular, the similarity of its oxidized form, dihydroascorbic acid, to glucose

Since tumor have increased requirement for glucose [67], transport of dehydroascorbate into the cancer cells via glucose transport molecules and ascorbate through sodium-dependent transporter may be elevated

Increased accumulation of ascorbic acid in the tumor site was supported by measurements of the level of ascorbic acid in tumors in animal experiments

Regarding inflammation, 73±13% of subjects (95% confidence) showed a reduction in CRP levels during therapy. This was an even more dramatic 86±13% (95% confidence) in subjects who started therapy with CRP levels above 10 mg/L

IVC therapy appears to reduce CRP levels in cancer patients.

CRP concentrations directly correlate with disease activity in many cases and can contribute to disease progression through a range of pro-inflammatory properties.

Being an exquisitely sensitive marker of systemic inflammation and tissue damage, CRP is very useful in screening for organic disease and monitoring treatment responses

ncreases in CRP concentrations have been associated with poorer prognosis of survival in cancer patients, particularly with advance disease independent of tumor stage

patients with advanced malignancies may have lower level of ascorbic acid in tissue, creating a higher demand for the vitamin C

patients treated by IVC with follow-up several year showed that suppression of inflammation in cancer patients by high-dose IVC is feasible and potentially beneficial

Inflammation is a marker of high cancer risk, and poor treatment outcome

The subjects with highly elevated CRP concentrations have a three-fold elevation “all-cause” mortality risk and a twenty-eight fold increase in cancer mortality risk

cancer patients may need higher doses to achieve a given plasma concentration.

patients with lower vitamin C levels may see more distribution of intravenously administered ascorbate into tissues and thus attain less in plasma.

When treating patients with IVC, the first treatment likely serves to replenish depleted tissue stores, if those subjects were vitamin C deficient at the beginning of the treatment. Then, in subsequent treatments, with increasing doses, higher plasma concentrations can be attained. On-going treatments serve to progressively reduce oxidative stress in cancer patients.

large doses given intravenously may result in maximum plasma concentrations of roughly 30 mM, a level that has been shown to be sufficient for preferential cytotoxicity against cancer cells

oral intake of vitamin C exceeded 200 mg administered once daily, it was difficult to increase plasma and tissue concentrations above roughly 200 μM.

the ketogenic diet may inhibit cancer progression in part by indirect dietary energy restriction

KD with HBO2T. Combining these therapies nearly doubled survival time in mice with metastatic cancer,

low carbohydrate or ketogenic diets promote weight loss in overweight individuals, they are also known to spare muscle wasting during conditions of energy restriction and starvation

dietary-induced therapeutic ketosis in a cancer patient would prevent muscle wasting similarly as it does with athletes undergoing intense exercise

when given as an adjuvant treatment to advanced cancer patients, the KD improves quality of life and enhances the efficacy of chemotherapy treatment in the clinic

The average age of FQ-induced tendinopathy is 64 years, with a male-to-female ratio of 2:1, and a 27-percent incidence of bilateral involvement

Although more than 95 percent of cases of tendinitis/rupture secondary to FQ involve the Achilles tendon, other reported sites of tendon involvement include the quadriceps, peroneus brevis, and rotator cuff

FQs demonstrate a 3.8-fold greater risk for development of Achilles tendinitis/rupture

a large population-based case control analysis, patients treated with FQs exhibited a substantially increased risk of developing tendon disorders overall (1.7-fold), tendon rupture (1.3-fold), and ATR (4.1-fold)

patients taking FQs with concurrent exposure to corticosteroids were found to experience a compounding effect on the risk of tendon rupture, specifically a 46-fold greater predisposition

Some authors have recommended that patients with a history of Achilles tendinitis and advanced age should not be prescribed FQ antibiotics

Approximately 50 percent of patients will recover within 30 days, with 25 percent of patients having symptoms persistent for longer than two months

The mean latency period between the start of FQ treatment and occurrence of tendinopathy has been reported to be a few hours to months, with a median onset of 6 days

The exact pathophysiology of FQ-induced tendinopathy remains elusive

it is possible that FQs have a direct cytotoxic effect on enzymes found in mammalian musculoskeletal tissue

It has been theorized that FQs disproportionately affect human tendons that have a limited capacity for repair, such as in older patients or structural compromise (i.e., pre-existing tendinopathy or trauma)

histopathological findings are similar to those observed in overuse conditions in athletes

Treatment with a FQ should be discontinued and physical therapy initiated

treatment should include rest and decreasing the physical load on the tendon.

Approximately 85 percent of patients present in less than one month

Because rupture can occur even late in the course of treatment or after discontinuation of FQ use, patients receiving a FQ should be counseled to seek medical attention immediately if symptoms, such as redness, pain, swelling, and stiffness, develop

FQs should be used cautiously in patients with risk factors associated with tendinitis, such as advanced age, history of tendon rupture, corticosteroid use, and/or acute or chronic renal dysfunction